AU734052B2

AU734052B2 - Nucleic acid and amino acid sequences relating to helicobacter pylori and vaccine compositions thereof

Info

Publication number: AU734052B2
Application number: AU50933/98A
Authority: AU
Inventors: Richard A. Alm; Douglas Smith
Original assignee: Astra AB
Current assignee: AstraZeneca AB
Priority date: 1996-10-28
Filing date: 1997-10-28
Publication date: 2001-05-31
Anticipated expiration: 2017-10-28
Also published as: IL129397A0; AR009600A1; SA98180918A; EP0973394A1; AU5093398A; EE9900176A; BR9712587A; TR199900940T2; EP0973394A4; CN1235513A; KR20000052831A; CA2265523A1; NO991995D0; ID22065A; IS5005A; PL333169A1; NZ334568A; JP2001504329A; SK34699A3; WO1998018323A1

Description

WO 98/18323 PCT/US97/19575 -1- NUCLEIC ACID AND AMINO ACID SEQUENCES RELATING TO HELICOBACTER PYLORI AND VACCINE COMPOSITIONS THEREOF Background of the Invention Helicobacter pylori is a gram-negative, S-shaped, microaerophilic bacterium that was discovered and cultured from a human gastric biopsy specimen. (Warren, J.R. and B. Marshall, (1983) Lancet 1: 1273-1275; and Marshall et al., (1984) Microbios Lett. 83-88). H. pylori has been strongly linked to chronic gastritis and duodenal ulcer disease. (Rathbone et. al., (1986) Gut 27: 635-641). Moreover, evidence is accumulating for an etiologic role of H. pylori in nonulcer dyspepsia, gastric ulcer disease, and gastric adenocarcinoma. (Blaser M. (1993) Trends Microbiol. 1: 255- 260). Transmission of the bacteria occurs via the oral route, and the risk of infection increases with age. (Taylor, D.N. and M. J. Blaser, (1991) Epidemiol. Rev 13: 42-50).

H. pylori colonizes the human gastric mucosa, establishing an infection that usually persists for decades. Infection by H. pylori is prevalent worldwide. Developed countries have infection rates over 50% of the adult population, while developing countries have infection rates reaching 90% of the adults over the age of 20. (Hopkins R. J. and J. G. Morris (1994) Am. J. Med. 97: 265-277).

The bacterial factors necessary for colonization of the gastric environment, and for virulence of this pathogen, are poorly understood. Examples of the putative virulence factors include the following: urease, an enzyme that may play a role in neutralizing gastric acid pH (Eaton et al., (1991) Infect. Immunol. 59: 2470-2475; Ferrero, R.L. and A. Lee (1991) Microb. Ecol. Hith. Dis. 4: 121-134: Labigne et al., (1991) J. Bacteriol. 173: 1920-1931); the bacterial flagellar proteins responsible for motility across the mucous layer. (Hazell et al., (1986) J. Inf. Dis. 153: 658-663; Leying et al., (1992) Mol. Microbiol. 6: 2863-2874; and Haas et al., (1993) Mol. Microbiol. 8: 753-760); Vac A, a bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells (Schmitt, W. and R. Haas, (1994) Molecular Microbiol. 12(2): 307-319); and several gastric tissue-specific adhesins. (Boren et al., (1993) Science 262: 1892- 1895; Evans et al., (1993) J. Bacteriol. 175: 674-683; and Falk et al., (1993) Proc. Natl.

Acad Sci. USA 90: 2035-203).

Numerous therapeutic agents are currently available that eradicate H. pylori infections in vitro. (Huesca et. al., (1993) Zbl. Bakt. 280: 244-252; Hopkins, R. J. and J.

G. Morris, supra). However, many of these treatments are suboptimally effective in vivo because of bacterial resistance, altered drug distribution, patient non-compliance or poor drug availabilty. (Hopkins, R. J. and J. G. Morris, supra). Treatment with antibiotics combined with bismuth are part of the standard regime used to treat H. pylori infection.

WO 98/18323 PCT/US97/19575 -2- (Malfertheiner, P. and J. E. Dominguez-Munoz (1993) Clinical Therapeutics 15 Supp.

B: 37-48). Recently, combinations of a proton pump inhibitors and a single antibiotic have been shown to ameliorate duodenal ulcer disease. (Malfertheiner, P. and J. E.

Dominguez-Munoz supra). However, methods employing antibiotic agents can have the problem of the emergence of bacterial strains which are iesistant to these agents.

(Hopkins, R. J. and J. G. Morris, supra). These limitations demonstrate that new more effective methods are needed to combat H. pylori infections in vivo. In particular, the design of new vaccines that may prevent infection by this bacterium is highly desirable.

Summary of the Invention This invention relates to novel genes, genes encoding polypeptides such as bacterial surface proteins, from the organism Helicobacter pylori pylori), and other related genes, their products, and uses thereof. The nucleic acids and peptides of the present invention have utility for diagnostic and therapeutics for H. pylori and other Helicobacter species. They can also be used to detect the presence of H. pylori and other Helicobacter species in a sample; and for use in screening compounds for the ability to interfere with the H. pylori life cycle or to inhibit H. pylori infection. More specifically, this invention features compositions of nucleic acids corresponding to entire coding sequences of H. pylori proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from H. pylori proteins to block protein translation, and methods for producing H. pylori proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect H. pylori infection. In addition, vaccine compositions and methods for the protection or treatment of infection by H.

pylori are within the scope of this invention.

Detailed Description of the Drawings Figure 1 is a bar graph that depicts the antibody titer in serum of mice following immunization with specific H. pylori antigens.

Figure 2 is a bar graph that depicts the antibody titer in mucous of mice following immunization with specific H. pylori antigens.

Figure 3 is a bar graph that depicts therapeutic immunization ofH. pylori infected mice with specific antigens dissolved in HEPES buffer.

Figure 4 is a bar graph that depicts therapeutic immunization of H. pylori infected mice with specific antigens dissolved in buffer containing DOC.

WO 98/18323 PCT/US97/19575 Figure 5 depicts the amino acid sequence alignment in a portion of the sequence of five H. pylori proteins (depicted in the single letter amino acid code; shown Nterminal to C-terminal, left to right).

Figure 6 depicts the amino acid sequence alignment in a portion of the sequence of four H. pylori proteins (depicted in the single letter amrino acid code; shown Nterminal to C-terminal, left to right).

Figure 7 depicts the amino acid sequence alignment in a portion of the sequence of two H. pylori proteins (depicted in the single letter amino acid code; shown Nterminal to C-terminal, left to right).

Figure 8 depicts the amino acid sequence alignment in a portion of the sequence of two H. pylori proteins (depicted in the single letter amino acid code; shown Nterminal to C-terminal, left to right).

Detailed Description of the Invention In one aspect, the invention features a recombinant or substantially pure preparation of H. pylori polypeptide of SEQ ID NO: 74. The invention also includes substantially pure nucleic acid encoding an H. pylori polypeptide of SEQ ID NO: 74, such nucleic acid is contained in SEQ ID NO: 1. The H. pylori polypeptide sequences of the invention described herein are contained in the Sequence Listing, and the nucleic acids encoding H. pylori polypeptides of the invention are contained in the Sequence Listing.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 2.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 76, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 3.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 77, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 4.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 78, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 79, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 6.

WO 98/18323 PCT/US97/19575 -4- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 7.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 81, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 8.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 82, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 9.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 83, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 84, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 11.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 12.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 86, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 13.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 87, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 14.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 88, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 89, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 16.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 17.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 91, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 18.

WO 98/18323 PCT/US97/19575 In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 92, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 19.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 93, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 94, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 21.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 22.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 96, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 23.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 97, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 24.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 98, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 99, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 26.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 100, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 27.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 101, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 28.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 102, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 29.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 103, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: WO 98/18323 PCT/US97/19575 -6- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 104, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 31.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 105, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 32.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 106, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 33.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 107, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 34.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 108, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 109, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 36.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 110, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 37.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 111, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 38.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 112, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 39.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 113, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 114, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 41.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 115, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 42.

WO 98/18323 PCT/US97/19575 -7- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 116, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO:43.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 117, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 44.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 118, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 119, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 46.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 120, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 47.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 121, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 48.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 122, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 49.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 123, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 124, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 51.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 125, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 52.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 126, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 53.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 127, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 54.

WO 98/18323 PCTIUS97/19575 -8- In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 128, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 129, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 56.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 130, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 57.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 131, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 58.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 132, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 59.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 133, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 134, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 61.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 135, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 62.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 136, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 63.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 137, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 64.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 138, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 139, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 66.

WO 98/18323 PCT/US97/19575 -9- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 140, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 67.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 141, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 68.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 142, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 69.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 143, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 144, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 71.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 145, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 72.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 146, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 73.

Particularly perferred is an isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cell envelope polypeptide or a fragment thereof. Such nucleic acid is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: SEQ ID NO: 48, SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, SEQ ID NO: 71, SEQ ID NO: 17, SEQ ID NO: 57, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, and SEQ ID NO: 21.

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a fragment thereof encoded by the nucleic acid selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, and SEQ ID NO: 48.

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof encoded by the nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: WO 98/18323 PCT/US97/19575 SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71.

In another embodiment, the H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a Cterminal tyrosine cluster or a fragment thereof encoded by the nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 1l,and SEQ ID NO:71.

In yet another embodiment, the H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof encoded by the nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, and SEQ ID NO: 58.

Particularly preferred is an isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori secreted polypeptide or a fragment thereof. Such nucleic acid is selected from the group consisting of SEQ ID NO: 72, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40. SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 53, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, and SEQ ID NO: 68.

Particularly preferred is an isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cellular polypeptide or a fragment thereof. Such nucleic acid is selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 20, SEQ ID NO: 23. SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 73.

Particularly preferred is a purified or isolated H. pylori cell envelope polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID WO 98/18323 PCT/US97/19575 -11- NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 130, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, and SEQ ID NO: 94.

In another embodiment, the H pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, and SEQ ID NO: 121.

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, and SEQ ID NO: 130.

In another embodiment, the H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a Cterminal tyrosine cluster or a fragment thereof selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, and SEQ ID NO:144.

In another embodiment, the H pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof selected from the group consisting of SEQ ID NO: 89. SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131.

Particularly preferred is a purified or isolated H pylori secreted polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 95, SEQ ID NO: 102. SEQ ID NO: 104, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, and SEQ ID NO: 141.

Particularly preferred is a purified or isolated H. pylori cellular polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, SEQ ID NO: 96, SEQ ID NO: 97, SEQ WO 98/18323 PCT/US97/19575 -12- ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 142, SEQ ID NO: 143, and SEQ ID NO: 146.

In another aspect, the invention pertains to any individual H. pylori polypeptide member or nucleic acid encoding such a member from the above-identified groups of H.

pylori polypeptides.

In another aspect, the invention features nucleic acids capable of binding mRNA of H. pylori. Such nucleic acid is capable of acting as antisense nucleic acid to control the translation of mRNA of H. pylori. A further aspect features a nucleic acid which is capable of binding specifically to an H pylori nucleic acid. These nucleic acids are also referred to herein as complements and have utility as probes and as capture reagents.

In another aspect, the invention features an expression system comprising an open reading frame corresponding to H pylori nucleic acid. The nucleic acid further comprises a control sequence compatible with an intended host. The expression system is useful for making polypeptides corresponding to H. pylori nucleic acid.

In another aspect, the invention features a cell transformed with the expression system to produce H. pylori polypeptides.

In another aspect, the invention features a method of generating antibodies against H. pylori polypeptides which are capable of binding specifically to H. pylori polypeptides. Such antibodies have utility as reagents for immunoassays to evaluate the abundance and distribution of H. pylori-specific antigens.

In another aspect, the invention features a method of generating vaccines for immunizing an individual against H. pylori. The vaccination method includes: immunizing a subject with at least one H. pylori polypeptide according to the present invention, a surface or secreted polypeptide, or active portion thereof, and a pharmaceutically acceptable carrier. Such vaccines have therapeutic and/or prophylactic utilities.

In another aspect, the invention provides a method for generating a vaccine comprising a modified immunogenic H pylori polypeptide, a surface or secreted polypeptide, or active portion thereof, and a pharmacologically acceptable carrier.

In another aspect, the invention features a method of evaluating a compound, e.g.

a polypeptide, a fragment of a host cell polypeptide, for the ability to bind an H.

pylori polypeptide. The method includes: contacting the candidate compound with an H. pylori polypeptide and determining if the compound binds or otherwise interacts with an H. pylori polypeptide. Compounds which bind H. pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays can be performed in vitro or in vivo.

WO 98/18323 PCT/US97/19575 13- In another aspect, the invention features a method of evaluating a compound, e.g.

a polypeptide, a fragment of a host cell polypeptide. for the ability to bind an H.

pylori nucleic acid, DNA or RNA. The method includes: contacting the candidate compound with an H. pylori nucleic acid and determining if the compound binds or otherwise interacts with an H. pylori polypeptide. Compounds which bind H. pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays can be performed in vitro or in vivo.

The invention features H. pylori polypeptides. preferably a substantially pure preparation of an H. pylori polypeptide, or a recombinant H. pylori polypeptide. In preferred embodiments: the polypeptide has biological activity; the polypeptide has an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% identical or homologous to an amino acid sequence of the invention contained in the Sequence Listing, preferably it has about 65% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing, and most preferably it has about 92% to about 99% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide is at least 5, 10, 20, 50, 100, or 150 amino acid residues in length; the polypeptide includes at least 5, preferably at least 10. more preferably at least 20, more preferably at least 50, 100, or 150 contiguous amino acid residues of the invention contained in the Sequence Listing. In yet another preferred embodiment, the amino acid sequence which differs in sequence identity by about 7% to about 8% from the H. pylori amino acid sequences of the invention contained in the Sequence Listing is also encompassed by the invention.

In preferred embodiments: the H. pylori polypeptide is encoded by a nucleic acid of thle invention contained in the Sequence Listing, or by a nucleic acid having at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% homology with a nucleic acid of the invention contained in the Sequence Listing.

In a preferred embodiment, the subject H. pylori polypeptide differs in amino acid sequence at 1, 2, 3, 5, 10 or more residues from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that the H. pylori polypeptide exhibits an H. pylori biological activity, the H. pylori polypeptide retains a biological activity of a naturally occurring H. pylori polypeptide.

In preferred embodiments, the polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic WO 98/18323 PCT/US97/19575 -14- DNA 5' or 3' to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.

In yet other preferred embodiments, the H. pylori polypeptide is a recombinant fusion protein having a first H. pylori polypeptide portion and a second polypeptide portion, a second polypeptide portion having an amino acid sequence unrelated to H. pylori. The second polypeptide portion can be, any of glutathione-S-transferase, a DNA binding domain, or a polymerase activating domain. In preferred embodiment the fusion protein can be used in a two-hybrid assay.

Polypeptides of the invention include those which arise as a result of alternative transcription events, alternative RNA splicing events, and alternative translational and postranslational events.

The invention also encompasses an immunogenic component which includes at least one H. pylori polypeptide in an immunogenic preparation; the immunogenic component being capable of eliciting an immune response specific for the H. pylori polypeptide, a humoral response, an antibody response, or a cellular response. In preferred embodiments, the immunogenic component comprises at least one antigenic determinant from a polypeptide of the invention contained in the Sequence Listing.

In another aspect, the invention provides a substantially pure nucleic acid having a nucleotide sequence which encodes an H. pylori polypeptide. In preferred embodiments: the encoded polypeptide has biological activity; the encoded polypeptide has an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% homologous to an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide is at least 5, 10, 20, 50, 100, or 150 amino acids in length; the encoded polypeptide comprises at least 5, preferably at least 10, more preferably at least 20, more preferably at least 50, 100, or 150 contiguous amino acids of the invention contained in the Sequence Listing.

In preferred embodiments: the nucleic acid of the invention is that contained in the Sequence Listing; the nucleic acid is at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% homologous with a nucleic acid sequence of the invention contained in the Sequence Listing.

In a preferred embodiment, the encoded H. pylori polypeptide differs by amino acid substitution, addition or deletion of at least one amino acid residue) in amino acid sequence at 1, 2, 3, 5, 10 or more residues, from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that: the H.

WO 98/18323 PCT/US97/19575 pylori encoded polypeptide exhibits a H. pylori biological activity, the encoded H pylori enzyme retains a biological activity of a naturally occurring H pylori.

In preferred embodiments, the encoded polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5' or 3' to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.

In preferred embodiments, the subject H. pylori nucleic acid will include a transcriptional regulatory sequence, e.g. at least one of a transcriptional promoter or transcriptional enhancer sequence, operably linked to the H. pylori gene sequence, e.g., to render the H. pylori gene sequence suitable for expression in a recombinant host cell.

In yet a further preferred embodiment, the nucleic acid which encodes an H.

pylori polypeptide of the invention, hybridizes under stringent conditions to a nucleic acid probe corresponding to at least 8 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least 12 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least 20 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least 40 consecutive nucleotides of the invention contained in the Sequence Listing.

In a preferred embodiment, the nucleic acid encodes a peptide which differs by at least one amino acid residue from the sequences of the invention contained in the Sequence Listing.

In a preferred embodiment, the nucleic acid differs by at least one nucleotide from a nucleotide sequence of the invention contained in the Sequence Listing which encodes amino acids of the invention contained in the Sequence Listing.

In another aspect, the invention encompasses: a vector including a nucleic acid which encodes an H. pylori polypeptide or an H. pylori polypeptide variant as described herein, a host cell transfected with the vector; and a method of producing a recombinant H. pylori polypeptide or H. pylori polypeptide variant; including culturing the cell, e.g., in a cell culture medium, and isolating the H. pylori or H. pylori polypeptide variant, from the cell or from the cell culture medium.

In another aspect, the invention features, a purified recombinant nucleic acid having at least 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99% homology with a sequence of the invention contained in the Sequence Listing.

The invention also provides a probe or primer which includes a substantially purified oligonucleotide. The oligonucleotide includes a region of nucleotide sequence which hybridizes under stringent conditions to at least 8 consecutive nucleotides of sense or antisense sequence of the invention contained in the Sequence Listing, or WO 98/18323 PCT/US97/19575 -16naturally occurring mutants thereof. In preferred embodiments, the probe or primer further includes a label group attached thereto. The label group can be, a radioisotope, a fluorescent compound, an enzyme, and/or an enzyme co-factor.

Preferably the oligonucleotide is at least 8 and less than 10, 20, 30, 50, 100, or 150 nucleotides in length.

The invention also provides an isolated H. pylori polypeptide which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid contained in the Sequence Listing.

The invention further provides nucleic acids, RNA or DNA, encoding a polypeptide of the invention. This includes double stranded nucleic acids as well as coding and antisense single strands.

The H. pylori strain, from which genomic sequences have been sequenced, has been deposited in the American Type Culture Collection (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) as strain HP-J99.

Included in the invention are: allelic variations; natural mutants; induced mutants; proteins encoded by DNA that hybridizes under high or low stringency conditions to a nucleic acid which encodes a polypeptide of the invention contained in the Sequence Listing (for definitions of high and low stringency see Current Protocols in Molecular Biology, John Wiley Sons, New York, 1989, 6.3.1 6.3.6 and 6.4.1-6.4.10, hereby incorporated by reference); and, polypeptides specifically bound by antisera to H pylori polypeptides, especially by antisera to an active site or binding domain of H.

pylori polypeptide. The invention also includes fragments. preferably biologically active fragments. These and other polypeptides are also referred to herein as H. pylori polypeptide analogs or variants.

Putative functions have been determined for several of the H. pylori polypeptides of the invention, as shown in Table 1.

Accordingly, uses of the claimed H. pylori polypeptides based on these identified functions, as well as other functions as described herein, are also within the scope of the invention.

In addition, the present invention encompasses H pylori polypeptides characterized as shown in Table 1 below, including: H. pylori cell envelope proteins, H.

pylori secreted proteins, and H. pylori cellular proteins. Members of these groups were identified by BLAST homology searches and by searches for secretion signal or transmembrane protein motifs. Polypeptides related by significant homology to the polypeptides of Table 1 are also considered to be classified in the manner of the homologs shown in Table 1.

WO 98/18323 WO 9818323PCT/US97/19575 17- TABLE 1 ORFName and Group nt SeqID aa SeqID A. CELL ENVELOPE A. 1 Inner membrane proteins____ O2gel 1622 23494043 f1 6 3 76 hp5p15212_13095752_-c3_136 25 98 06ep30223 20173437 fi37 48 121 A.2 Outer membrane proteins 05ee1 0816-14495437f2 13 10 83' A.2.1 Terminal phe residue 06ep11509 35954752 f2 -1 16 89 06ep10615 14495437_f3_ 47 45 118 03ae10804 14495437 c2 38 35 108 05ae30220_917200_c3_172 37 110 04cp1 1202_23646885_f2_26 7 05ep10815 16131925 c2 97 39 112 09cp61003 5860877_f2_23 55 128 09ae10512_48768_c3_67 18 91 09cp11003 5860877 f3 7 19 92 hp6e12267 30478562 f3 33 28 101 06cp30603_34174212_c3_71 30 103 09cp10224_1962590_f3M_-31 52 125 09cp61003_30478562_c3_106 54 127 11ae80818_1 05531 92f22_16 56 129 11ee11408_10584582_c3_51 58 131 A.2.2 Terminal phe residue and Cterminal tyrosine cluster Olael200l_116018_c2_40 1 74 06ap10609_116018_c3_50 42 115 06cp30603 4687507 fi 9 14 87 06cp30603 4687507 fM 7 43 116 05ee10816 36126938 f3 16 11 84 01cp20708 4960952 ci43 71 144 A.3 Via 07ap80601_5083193_f3_8 17 11ap20714_4797137_f3M_-45 57 130 A.4 Other cell envelope proteins 04ap12016_25501501_-fi_-1 5 78 04cp1 1202_20415937_f2_25 6 79 04ee11108 -3906963_fi_7 8 81 29ep10720 25501501 c2 33 21 94 B. SECRETED PROTEINS hp3e10342 22448587 c2 15 72 145 hp5p15212 24276587 fi2 32 105 09ce10413 35336707f2 9 511 124 WO 98/18323 WO 9818323PCTIIJS97/19575 18- 01ae12001 32462543 c2 43 2 03ee11215 1416312 c3 35 4 77 05ae30220 14570443 c2 94 9 82 06cp30603 2772578 ci 46 13 86 29ep10720 289077f2 12 22 03ee1 1215 22542803 fi7 29 102 09ae10512 3166040 ci40 31 104 01ce11104_10742963_c2_12 33 106 02ge10116 36335436 f3M 66 34 107 04ep41903 11876461 fl 4 36 109 05ce10208 23631292 fl 6 38 ill 05ep10815 22447252 c3 110 40 113 05ep10815 30283516 -c3 -109 41 114 06ee30709 33851038 c3 30 44 117 06ep11202 21687842 -c3 -35 46 119 06ep30223 2774062 fl 33 49 122 09cp10713 23912707 ci26 53 126 lleell408 4882318 f3 24 59 132 hp4e13394_5908553_fl_1 61 134 hp4e53394_1416312_c3_119 62 135 hp5e15211 24328910 c3 38 63 136 hp6p10606_23493756_ci_21 65 138 hp6p22217 23564012 fi5 66 139 hp6p22217 272058 fi2 67 140 hp6p22217 2922143 f2Q 9 68 141 C. OTHER CELLULAR PROTEINS 06ap11119 14726542 f3 21 12 06ee10709 6136430 ci11 15 88 12ap10605 14094816 cl 5 20, 93 hp2p10272_34042518_fl_2 23 96 hp5e15211_25411557_ci_-22 24 97 hp5p15641_3907968_fi13 26 99 hp6e10967_6576382f3-9 27 100 06ep11202 4569693 c2 28 47 120 06ep30223_3930468_ci110 50 123 hp2elO9ll_960952_c2_86 60 133 hp6plO5O9_146422 1 7_c2_-17 64 137 hp6p80503_20964382_22_11 69 142 hp7e10192_5917593fi_2 70 143 hp6p10509 14642217 c3 25 73 146 [In Table 1, "nt" represents nucleotide Seq. ID number and "aa" represents Seq. ID number] amino acid Definitions The terms "purified polypeptide" and "isolated polypeptide" and "a substantially pure preparation of a polypeptide" are used interchangeably herein and, as used herein, WO 98/18323 PCT/US97/19575 -19from other proteins, lipids, and nucleic acids with which it naturally occurs. Preferably, the polypeptide is also separated from substances, antibodies or gel matrix, e.g., polyacrylamide, which are used to purify it. Preferably, the polypeptide constitutes at least 10, 20, 50 70, 80 or 95% dry weight of the purified preparation. Preferably, the preparation contains: sufficient polypeptide to allow protein sequencing; at least 1, or 100 jtg of the polypeptide; at least 1, 10, or 100 mg of the polypeptide. Furthermore, the terms "purified polypeptide" and "isolated polypeptide" and "a substantially pure preparation of a polypeptide," as used herein, refer to both a polypeptide obtained from nature or produced by recombinant DNA techniques as described herein.

For example, an "isolated" or "purified" protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the H. pylori protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language "substantially free of cellular material" includes preparations of H. pylori protein in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly produced. In one embodiment, the language "substantially free of cellular material" includes preparations of H. pylori protein having less than about 30% (by dry weight) of non-H, pylori protein (also referred to herein as a "contaminating protein"), more preferably less than about 20% of non-H pylori protein, still more preferably less than about 10% of non-H. pylori protein, and most preferably less than about 5% non-H pylori protein. When the H. pylori protein or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, culture medium represents less than about 20%, more preferably lessthan about 10%, and most preferably less than about 5% of the volume of the protein preparation.

The language "substantially free of chemical precursors or other chemicals" includes preparations of H. pylori protein in which the protein is separated from chemical precusors or other chemicals which are involved in the synthesis of the protein.

In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations of H. pylori protein having less than about 30% (by dry weight) of chemical precursors or non-H. pylori chemicals, more preferably less than about 20% chemical precursors or non-H, pylori chemicals, still more preferably less than about 10% chemical precursors or non-H pylori chemicals, and most preferably less than about 5% chemical precursors or non-H. pylori chemicals.

A purified preparation of cells refers to, in the case of plant or animal cells, an in vitro preparation of cells and not an entire intact plant or animal. In the case of cultured WO 98/18323 PCT/US97/19575 cells or microbial cells, it consists of a preparation of at least 10% and more preferably of the subject cells.

A purified or isolated or a substantially pure nucleic acid, a substantially pure DNA, (are terms used interchangeably herein) is a nucleic acid which is one or both of the following: not immediately contiguous with both of the coding sequences with which it is immediately contiguous one at the 5' end and one at the 3' end) in the naturally-occurring genome of the organism from which the nucleic acid is derived; or which is substantially free of a nucleic acid with which it occurs in the organism from which the nucleic acid is derived. The term includes, for example, a recombinant DNA which is incorporated into a vector, into an autonomously replicating plasmid or virus, or into the genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule a cDNA or a genomic DNA fragment produced by PCR or restriction endonuclease treatment) independent of other DNA sequences. Substantially pure DNA also includes a recombinant DNA which is part of a hybrid gene encoding additional H. pylori DNA sequence.

A "contig" as used herein is a nucleic acid representing a continuous stretch of genomic sequence of an organism.

An "open reading frame", also referred to herein as ORF, is a region of nucleic acid which encodes a polypeptide. This region may represent a portion of a coding sequence or a total sequence and can be determined from a stop to stop codon or from a start to stop codon.

As used herein, a "coding sequence" is a nucleic acid which is transcribed into messenger RNA and/or translated into a polypeptide when placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a translation start codon at the five prime terminus and a translation stop code at the three prime terminus. A coding sequence can include but is not limited to messenger RNA, synthetic DNA, and recombinant nucleic acid sequences.

A "complement" of a nucleic acid as used herein referes to an anti-parallel or antisense sequence that participates in Watson-Crick base-pairing with the original sequence.

A "gene product" is a protein or structural RNA which is specifically encoded by a gene.

As used herein, the term "probe" refers to a nucleic acid, peptide or other chemical entity which specifically binds to a molecule of interest. Probes are often associated with or capable of associating with a label. A label is a chemical moiety capable of detection. Typical labels comprise dyes, radioisotopes, luminescent and chemiluminescent moieties, fluorophores, enzymes, precipitating agents, amplification WO 98/18323 PCT/US97/19575 -21sequences, and the like. Similarly, a nucleic acid, peptide or other chemical entity which specifically binds to a molecule of interest and immobilizes such molecule is referred herein as a "capture ligand". Capture ligands are typically associated with or capable of associating with a support such as nitro-cellulose, glass, nylon membranes, beads, particles and the like. The specificity of hybridization is dependent on conditions such as the base pair composition of the nucleotides, and the temperature and salt concentration of the reaction. These conditions are readily discernable to one of ordinary skill in the art using routine experimentation.

Homologous refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. When a position in both of the two compared sequences is occupied by the same base or amino acid monomer subunit, e.g., if a position in each of two DNA molecules is occupied by adenine, then the molecules are homologous at that position. The percent of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared x 100. For example, if 6 of of the positions in two sequences are matched or homologous then the two sequences are homologous. By way of example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally, a comparison is made when two sequences are aligned to give maximum homology.

Nucleic acids are hybridizable to each other when at least one strand of a nucleic acid can anneal to the other nucleic acid under defined stringency conditions.

Stringency of hybridization is determined by: the temperature at which hybridization and/or washing is performed; and the ionic strength and polarity of the hybridization and washing solutions. Hybridization requires that the two nucleic acids contain complementary sequences; depending on the stringency of hybridization, however, mismatches may be tolerated. Typically, hybridization of two sequences at high stingency (such as, for example, in a solution of .SX SSC, at 650 C) requires that the sequences be essentially completely homologous. Conditions of intermediate stringency (such as, for example, 2X SSC at 65 C) and low stringency (such as, for example 2X SSC at 55' require correspondingly less overall complementarity between the hybridizing sequences. (IX SSC is 0.15 M NaCI, 0.015 M Na citrate). A preferred, non-limiting example of stringent hybridization conditions are hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45 0 C, followed by one or more washes in 0.2 X SSC, 0.1% SDS at 50-650C.

The terms peptides, proteins, and polypeptides are used interchangeably herein.

WO 98/18323 PCT/US97/19575 22- As used herein, the term "surface protein" refers to all surface accessible proteins, e.g. inner and outer membrane proteins, proteins adhering to the cell wall, and secreted proteins.

A polypeptide has H. pylori biological activity if it has one, two and preferably more of the following properties: if when expressed in the course of an H. pylori infection, it can promote, or mediate the attachment of H pylori to a cell; it has an enzymatic activity, structural or regulatory function characteristic of an H. pylori protein; the gene which encodes it can rescue a lethal mutation in an H. pylori gene; or it is immunogenic in a subject. A polypeptide has biological activity if it is an antagonist, agonist, or super-agonist of a polypeptide having one of the above-listed properties.

A biologically active fragment or analog is one having an in vivo or in vitro activity which is characteristic of the H. pylori polypeptides of the invention contained in the Sequence Listing, or of other naturally occurring H. pylori polypeptides, one or more of the biological activities described herein. Especially preferred are fragments which exist in vivo, fragments which arise from post transcriptional processing or which arise from translation of alternatively spliced RNA's. Fragments include those expressed in native or endogenous cells as well as those made in expression systems, in CHO cells. Because peptides such as H pylori polypeptides often exhibit a range of physiological properties and because such properties may be attributable to different portions of the molecule, a useful H. pylori fragment or H. pylori analog is one which exhibits a biological activity in any biological assay for H. pylori activity. Most preferably the fragment or analog possesses 10%, preferably 40%, more preferably 80% or 90% or greater of the activity of H. pylori, in any in vivo or in vitro assay.

Analogs can differ from naturally occurring H pylori polypeptides in amino acid sequence or in ways that do not involve sequence, or both. Non-sequence modifications include changes in acetylation, methylation, phosphorylation, carboxylation, or glycosylation. Preferred analogs include H. pylori polypeptides (or biologically active fragments thereof) whose sequences differ from the wild-type sequence by one or more conservative amino acid substitutions or by one or more non-conservative amino acid substitutions, deletions, or insertions which do not substantially diminish the biological activity of the H. pylori polypeptide. Conservative substitutions typically include the substitution of one amino acid for another with similar characteristics, substitutions within the following groups: valine, glycine; glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. Other conservative substitutions can be made in view of the table below.

WO 98/18323 WO 9818323PCTIUS97/19575 23 TABLE 2 CONSERVATIVE AMINO ACID REPLACEMENTS For Amino Acid Code Replace with any of Alanine A D-Ala, Gly, beta-Ala, L-Cys, D-Cys Arginine R D-Arg, Lys, D-Lys, homo-Arg, D-homo-Arg, Met, Ile, D-Met, D-Ile. Om, D-Orn.

Asparagine N D-Asn, Asp, D-Asp, Glu. D-Giu, Gln, D-Gln Aspartic Acid D D-Asp, D-Asn, Asn, Giu, D-Glu, Gin, D-Gln Cysteine C D-Cys, S-Me-Cys, Met, D-Met, Thr, D-Thr Glutamine Q D-Gln, Asn. D-Asn. Glu. D-Glu, Asp, D-Asp Glutamic Acid E D-Glu, D-Asp. Asp, Asn, D-Asn, Gin, D-Gin Glycine G Ala, D-Ala, Pro, D-Pro, 13-Ala, Acp Isoleucine I D-Ile, Val, D-Val, Leu, D-Leu, Met, D-Met Leucine L D-Leu, Val, D-Val, Leu, D-Leu, Met, D-Met Lysine K D-Lys, Arg, D-Arg, homo-Arg, D-homo-Arg, Met, D- Met, le, D-Ile, Omn, D-Orn Methionine M D-Met, S-Me-Cys, Ile, D-Ile, Leu, D-Leu. Val. D-Val Phenylalanine F D-Phe, Tyr, D-Thr, L-Dopa, His, D-His, Tmp, D-Trp, Trans-3 or 5-phenyiproline, cis-3 ,4, Proline IP D-Pro, L-I-thioazolidine-4-carboxylic acid, D-or L-I oxazolidine-4-carboxylic acid Serine S D-Ser, Thr, D-Thr, allo-Thr, Met, D-Met, Met(O), L-Cys, D-Cys Threonine T D-Thr, Ser, D-Ser, allo-Thr, Met, D-Met, Met(O), D-Met(O), Val, D-Val Tyrosine Y D-Tyr, Phe, D-Phe, L-Dopa, His, D-His Valine V D-Val, Leu, D-Leu, Ile, D-Iie, Met, D-Met WO 98/18323 PCT/US97/19575 -24- Other analogs within the invention are those with modifications which increase peptide stability; such analogs may contain, for example, one or more non-peptide bonds (which replace the peptide bonds) in the peptide sequence. Also included are: analogs that include residues other than naturally occurring L-amino acids, D-amino acids or non-naturally occurring or synthetic amino acids, P or y amino acids; and cyclic analogs.

As used herein, the term "fragment", as applied to an H. pylori analog, will ordinarily be at least about 20 residues, more typically at least about 40 residues, preferably at least about 60 residues in length. Fragments ofH. pylori polypeptides can be generated by methods known to those skilled in the art. The ability of a candidate fragment to exhibit a biological activity of H. pylori polypeptide can be assessed by methods known to those skilled in the art as described herein. Also included are H.

pylori polypeptides containing residues that are not required for biological activity of the peptide or that result from alternative mRNA splicing or alternative protein processing events.

An "immunogenic component" as used herein is a moiety, such as an H. pylori polypeptide, analog or fragment thereof, that is capable of eliciting a humoral and/or cellular immune response in a host animal alone or in combination with an adjuvant.

An "antigenic component" as used herein is a moiety, such as an H. pylori polypeptide, analog or fragment thereof, that is capable of binding to a specific antibody with sufficiently high affinity to form a detectable antigen-antibody complex.

As used herein, the term "transgene" means a nucleic acid (encoding, one or more polypeptides), which is partly or entirely heterologous, foreign, to the transgenic animal or cell into which it is introduced, or. is homologous to an endogenous gene of the transgenic animal or cell into which it is introduced, but which is designed to be inserted, or is inserted, into the cell's genome in such a way as to alter the genome of the cell into which it is inserted it is inserted at a location which differs from that of the natural gene or its insertion results in a knockout). A transgene can include one or more transcriptional regulatory sequences and any other nucleic acid, such as introns, that may be necessary for optimal expression of the selected nucleic acid, all operably linked to the selected nucleic acid, and may include an enhancer sequence.

As used herein, the term "transgenic cell" refers to a cell containing a transgene.

As used herein, a "transgenic animal" is any animal in which one or more, and preferably essentially all, of the cells of the animal includes a transgene. The transgene can be introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by a process of transformation of competent cells or by microinjection or by infection with a WO 98/18323 PCT/US97/19575 recombinant virus. This molecule may be integrated within a chromosome, or it may be extrachromosomally replicating DNA.

The term "antibody" as used herein is intended to include fragments thereof which are specifically reactive with H. pylori polypeptides.

As used herein, the term "cell-specific promoter" means a DNA sequence that serves as a promoter, regulates expression of a selected DNA sequence operably linked to the promoter, and which effects expression of the selected DNA sequence in specific cells of a tissue. The term also covers so-called "leaky" promoters, which regulate expression of a selected DNA primarily in one tissue, but cause expression in other tissues as well.

Misexpression, as used herein, refers to a non-wild type pattern of gene expression. It includes: expression at non-wild type levels, over or under expression; a pattern of expression that differs from wild type in terms of the time or stage at which the gene is expressed, increased or decreased expression (as compared with wild type) at a predetermined developmental period or stage; a pattern of expression that differs from wild type in terms of decreased expression (as compared with wild type) in a predetermined cell type or tissue type; a pattern of expression that differs from wild type in terms of the splicing size, amino acid sequence, posttransitional modification, or biological activity of the expressed polypeptide; a pattern of expression that differs from wild type in terms of the effect of an environmental stimulus or extracellular stimulus on expression of the gene, a pattern of increased or decreased expression (as compared with wild type) in the presence of an increase or decrease in the strength of the stimulus.

As used herein, "host cells" and other such terms denoting microorganisms or higher eukaryotic cell lines cultured as unicellular entities refers to cells which can become or have been used as recipients for a recombinant vector or other transfer DNA, and include the progeny of the original cell which has been transfected. It is understood by individuals skilled in the art that the progeny of a single parental cell may not necessarily be completely identical in genomic or total DNA compliment to the original parent, due to accident or deliberate mutation.

As used herein, the term "control sequence" refers to a nucleic acid having a base sequence which is recognized by the host organism to effect the expression of encoded sequences to which they are ligated. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include a promoter, ribosomal binding site, terminators, and in some cases operators; in eukaryotes, generally such control sequences include promoters, terminators and in some instances, enhancers. The term control sequence is intended to include at a WO 98/18323 PCT/US97/19575 -26minimum, all components whose presence is necessary for expression, and may also include additional components whose presence is advantageous, for example, leader sequences.

As used herein, the term "operably linked" refers to sequences joined or ligated to function in their intended manner. For example, a control sequence is operably linked to coding sequence by ligation in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequence and host cell.

The metabolism of a substance, as used herein, means any aspect of the, expression, function, action, or regulation of the substance. The metabolism of a substance includes modifications, covalent or non-covalent modifications of the substance. The metabolism of a substance includes modifications, covalent or noncovalent modification, the substance induces in other substances. The metabolism of a substance also includes changes in the distribution of the substance. The metabolism of a substance includes changes the substance induces in the distribution of other substances.

A "sample" as used herein refers to a biological sample, such as, for example, tissue or fluid isloated from an individual (including without limitation plasma, serum, cerebrospinal fluid, lymph, tears, saliva and tissue sections) or from in vitro cell culture constituents, as well as samples from the environment.

The practice of the invention will employ, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See Sambrook, Fritsch, and Maniatis, Molecular Cloning; Laboratory Manual 2nd ed. (1989); DNA Cloning, Volumes I and II (D.N Glover ed. 1985); Oligonucleotide Synthesis Gait ed, 1984); Nucleic Acid Hybridization Hames S.J. Higgins eds. 1984); the series, Methods in Enzymoloqy (Academic Press, Inc.), particularly Vol. 154 and Vol. 155 (Wu and Grossman, eds.) and PCR-A Practical Approach (McPherson, Quirke, and Taylor, eds., 1991).

I. Isolation of Nucleic Acids of H. pylori and Uses Therefor H. pylori Genomic Sequence This invention provides nucleotide sequences of the genome of H. pylori which thus comprises a DNA sequence library of H. pylori genomic DNA. The detailed description that follows provides nucleotide sequences of H. pylori, and also describes how the sequences were obtained and how ORFs and protein-coding sequences were WO 98/18323 PCT/US97/19575 -27identified. Also described are methods of using the disclosed H pylori sequences in methods including diagnostic and therapeutic applications. Furthermore, the library can be used as a database for identification and comparison of medically important sequences in this and other strains of H. pylori.

To determine the genomic sequence of H pylori, DNA was isolated from a strain of H. pylori (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) and mechanically sheared by nebulization to a median size of 2 kb. Following size fractionation by gel electrophoresis, the fragments were blunt-ended, ligated to adapter oligonucleotides, and cloned into each of different pMPX vectors (Rice et al., abstracts of Meeting of Genome Mapping and Sequencing, Cold Spring Harbor, NY, 5/11-5/15, 1994, p. 225) to construct a series of "shotgun" subclone libraries.

DNA sequencing was achieved using multiplex sequencing procedures essentially as disclosed in Church et al., 1988, Science 240:185; U.S. Patents No.

4,942,124 and 5,149,625). DNA was extracted from pooled cultures and subjected to chemical or enzymatic sequencing. Sequencing reactions were resolved by electrophoresis, and the products were transferred and covalently bound to nylon membranes. Finally, the membranes were sequentially hybridized with a series of labelled oligonucleotides complimentary to "tag" sequences present in the different shotgun cloning vectors. In this manner, a large number of sequences could be obtained from a single set of sequencing reactions. The cloning and sequencing procedures are described in more detail in the Exemplification.

Individual sequence reads obtained in this manner were assembled using the FALCONTM program (Church et al., 1994, Automated DNA Sequencing and Analysis, J.C. Venter, ed., Academic Press) and PHRAP Green, Abstracts of DOE Human Genome Program Contractor-Grantee Workshop V, Jan. 1996, p. 157). The average contig length was about 3-4 kb.

A variety of approaches are used to order the contigs so as to obtain a continuous sequence representing the entire H. pylori genome. Synthetic oligonucleotides are designed that are complementary to sequences at the end of each contig. These oligonucleotides may be hybridized to libaries of H. pylori genomic DNA in, for example, lambda phage vectors or plasmid vectors to identify clones that contain sequences corresponding to the junctional regions between individual contigs. Such clones are then used to isolate template DNA and the same oligonucleotides are used as primers in polymerase chain reaction (PCR) to amplify junctional fragments, the nucleotide sequence of which is then determined.

WO 98/18323 PCT/US97/19575 -28 The H. pylori sequences were analyzed for the presence of open reading frames (ORFs) comprising at least 180 nucleotides. As a result of the analysis of ORFs based on stop-to-stop codon reads, it should be understood that these ORFs may not correspond to the ORF of a naturally-occurring H. pylori polypeptide. These ORFs may contain start codons which indicate the initiation of protein synthesis of a naturallyoccurring H. pylori polypeptide. Such start codons within the ORFs provided herein can be identified by those of ordinary skill in the relevant art, and the resulting ORF and the encoded H. pylori polypeptide is within the scope of this invention. For example, within the ORFs a codon such as AUG or GUG (encoding methionine or valine) which is part of the initiation signal for protein synthesis can be identified and the ORF modified to correspond to a naturally-occurring H. pylori polypeptide. The predicted coding regions were defined by evaluating the coding potential of such sequences with the program GENEMARKTM (Borodovsky and Mclninch, 1993, Comp. Chem. 17:123).

Other H pylori Nucleic Acids The nucleic acids of this invention may be obtained directly from the DNA of the above referenced H pylori strain by using the polymerase chain reaction (PCR). See "PCR, A Practical Approach" (McPherson, Quirke, and Taylor, eds., IRL Press, Oxford, UK, 1991) for details about the PCR. High fidelity PCR can be used to ensure a faithful DNA copy prior to expression. In addition, the authenticity of amplified products can be checked by conventional sequencing methods. Clones carrying the desired sequences described in this invention may also be obtained by screening the libraries by means of the PCR or by hybridization of synthetic oligonucleotide probes to filter lifts of the library colonies or plaques as known in the art (see, Sambrook et al., Molecular Cloning, A Laboratory Manual 2nd edition, 1989, Cold Spring Harbor Press, NY).

It is also possible to obtain nucleic acids encoding H. pylori polypeptides from a cDNA library in accordance with protocols herein described. A cDNA encoding an H.

pylori polypeptide can be obtained by isolating total mRNA from an appropriate strain.

Double stranded cDNAs can then be prepared from the total mRNA. Subsequently, the cDNAs can be inserted into a suitable plasmid or viral bacteriophage) vector using any one of a number of known techniques. Genes encoding H. pylori polypeptides can also be cloned using established polymerase chain reaction techniques in accordance with the nucleotide sequence information provided by the invention. The nucleic acids of the invention can be DNA or RNA. Preferred nucleic acids of the invention are contained in the Sequence Listing.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemically synthesizing polydeoxynucleotides WO 98/18323 PCT/US97/19575 -29are known, including solid-phase synthesis which, like peptide synthesis, has been fully automated in commercially available DNA synthesizers (See Itakura et al. U.S.

Patent No. 4,598,049; Caruthers et al. U.S. Patent No. 4,458,066; and Itakura U.S.

Patent Nos. 4,401,796 and 4,373,071, incorporated by reference herein).

Nucleic acids isolated or synthesized in accordance with features of the present invention are useful, by way of example, without limitation, as probes, primers, capture ligands, antisense genes and for developing expression systems for the synthesis of proteins and peptides corresponding to such sequences. As probes, primers, capture ligands and antisense agents, the nucleic acid normally consists of all or part (approximately twenty or more nucleotides for specificity as well as the ability to form stable hybridization products) of the nucleic acids of the invention contained in the Sequence Listing. These uses are described in further detail below.

Probes A nucleic acid isolated or synthesized in accordance with the sequence of the invention contained in the Sequence Listing can be used as a probe to specifically detect H. pylori. With the sequence information set forth in the present application, sequences of twenty or more nucleotides are identified which provide the desired inclusivity and exclusivity with respect to H. pylori, and extraneous nucleic acids likely to be encountered during hybridization conditions. More preferably, the sequence will comprise at least twenty to thirty nucleotides to convey stability to the hybridization product formed between the probe and the intended target molecules.

Sequences larger than 1000 nucleotides in length are difficult to synthesize but can be generated by recombinant DNA techniques. Individuals skilled in the art will readily recognize that the nucleic acids, for use as probes, can be provided with a label to facilitate detection of a hybridization product.

Nucleic acid isolated and synthesized in accordance with the sequence of the invention contained in the Sequence Listing can also be useful as probes to detect homologous regions (especially homologous genes) of other Helicobacter species using appropriate stringency hybridization conditions as described herein.

Capture Ligand For use as a capture ligand. the nucleic acid selected in the manner described above with respect to probes, can be readily associated with a support. The manner in which nucleic acid is associated with supports is well known. Nucleic acid having twenty or more nucleotides in a sequence of the invention contained in the Sequence Listing have utility to separate H. pylori nucleic acid from the nucleic acid of each other and other organisms. Nucleic acid having twenty or more nucleotides in a sequence of the invention contained in the Sequence Listing can also have utility to separate other WO 98/18323 PCT/US97/19575 Helicobacter species from each other and from other organisms. Preferably, the sequence will comprise at least twenty nucleotides to convey stability to the hybridization product formed between the probe and the intended target molecules.

Sequences larger than 1000 nucleotides in length are difficult to synthesize but can be generated by recombinant DNA techniques.

Primers Nucleic acid isolated or synthesized in accordance with the sequences described herein have utility as primers for the amplification ofH. pylori nucleic acid. These nucleic acids may also have utility as primers for the amplification of nucleic acids in other Helicobacter species. With respect to polymerase chain reaction (PCR) techniques, nucleic acid sequences of 10-15 nucleotides of the invention contained in the Sequence Listing have utility in conjunction with suitable enzymes and reagents to create copies ofH. pylori nucleic acid. More preferably, the sequence will comprise twenty or more nucleotides to convey stability to the hybridization product formed between the primer and the intended target molecules. Binding conditions of primers greater than 100 nucleotides are more difficult to control to obtain specificity. High fidelity PCR can be used to ensure a faithful DNA copy prior to expression. In addition, amplified products can be checked by conventional sequencing methods.

The copies can be used in diagnostic assays to detect specific sequences, including genes from H. pylori and/or other Helicobacter species. The copies can also be incorporated into cloning and expression vectors to generate polypeptides corresponding to the nucleic acid synthesized by PCR, as is described in greater detail herein.

Antisense Nucleic acid or nucleic acid-hybridizing derivatives isolated or synthesized in accordance with the sequences described herein have utility as antisense agents to prevent the expression of H. pylori genes. These sequences also have utility as antisense agents to prevent expression of genes of other Helicobacter species.

In one embodiment, nucleic acid or derivatives corresponding to H. pylori nucleic acids is loaded into a suitable carrier such as a liposome or bacteriophage for introduction into bacterial cells. For example, a nucleic acid having twenty or more nucleotides is capable of binding to bacteria nucleic acid or bacteria messenger RNA.

Preferably, the antisense nucleic acid is comprised of 20 or more nucleotides to provide necessary stability of a hybridization product of non-naturally occurring nucleic acid and bacterial nucleic acid and/or bacterial messenger RNA. Nucleic acid having a sequence greater than 1000 nucleotides in length is difficult to synthesize but can be generated by recombinant DNA techniques. Methods for loading antisense nucleic acid in liposomes 4 l WO 98/18323 PCTIUS97/19575 -31 is known in the art as exemplified by U.S. Patent 4,241,046 issued December 23, 1980 to Papahadjopoulos et al.

II. Expression of H. pylori Nucleic Acids Nucleic acid isolated or synthesized in accordance with the sequences described herein have utility to generate polypeptides. The nucleic acid of the invention exemplified in the Sequence Listing or fragments of said nucleic acid encoding active portions of H. pylori polypeptides can be cloned into suitable vectors or used to isolate nucleic acid. The isolated nucleic acid is combined with suitable DNA linkers and cloned into a suitable vector.

The function of a specific gene or operon can be ascertained by expression in a bacterial strain under conditions where the activity of the gene product(s) specified by the gene or operon in question can be specifically measured. Alternatively, a gene product may be produced in large quantities in an expressing strain for use as an antigen, an industrial reagent, for structural studies, etc. This expression can be accomplished in a mutant strain which lacks the activity of the gene to be tested, or in a strain that does not produce the same gene product(s). This includes, but is not limited to other Helicobacter strains, or other bacterial strains such as E. coli, Norcardia, Corynebacterium, Campylobacter, and Streptomyces species. In some cases the expression host will utilize the natural Helicobacter promoter whereas in others, it will be necessary to drive the gene with a promoter sequence derived from the expressing organism an E. coli beta-galactosidase promoter for expression in E. coli).

To express a gene product using the natural H. pylori promoter, a procedure such as the following can be used. A restriction fragment containing the gene of interest, together with its associated natural promoter element and regulatory sequences (identified using the DNA sequence data) is cloned into an appropriate recombinant plasmid containing an origin of replication that functions in the host organism and an appropriate selectable marker. This can be accomplished by a number of procedures known to those skilled in the art. It is most preferably done by cutting the plasmid and the fragment to be cloned with the same restriction enzyme to produce compatible ends that can be ligated to join the two pieces together. The recombinant plasmid is introduced into the host organism by, for example, electroporation and cells containing the recombinant plasmid are identified by selection for the marker on the plasmid.

Expression of the desired gene product is detected using an assay specific for that gene product.

In the case of a gene that requires a different promoter, the body of the gene (coding sequence) is specifically excised and cloned into an appropriate expression WO 98/18323 PCT/US97/19575 -32plasmid. This subcloning can be done by several methods, but is most easily accomplished by PCR amplification of a specific fragment and ligation into an expression plasmid after treating the PCR product with a restriction enzyme or exonuclease to create suitable ends for cloning.

A suitable host cell for expression of a gene can be any procaryotic or eucaryotic cell. For example, an H. pylori polypeptide can be expressed in bacterial cells such as E.

coli, insect cells (baculovirus), yeast, or mammalian cells such as Chinese hamster ovary cell (CHO). Other suitable host cells are known to those skilled in the art.

Expression in eucaryotic cells such as mammalian, yeast, or insect cells can lead to partial or complete glycosylation and/or formation of relevant inter- or intra-chain disulfide bonds of a recombinant peptide product. Examples of vectors for expression in yeast S. cerivisae include pYepSecl (Baldari. et al., (1987) Embo J. 6:229-234), pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), and pYES2 (Invitrogen Corporation, San Diego, CA). Baculovirus vectors available for expression of proteins in cultured insect cells (SF 9 cells) include the pAc series (Smith et al., (1983) Mol. Cell Biol. 3:2156-2165) and the pVL series (Lucklow, and Summers, (1989) Virology 170:31-39). Generally, COS cells (Gluzman, (1981) Cell 23:175-182) are used in conjunction with such vectors as pCDM 8 (Aruffo, A. and Seed, (1987) Proc. Natl. Acad Sci. USA 84:8573-8577) for transient amplification/expression in mammalian cells, while CHO (dhfr- Chinese Hamster Ovary) cells are used with vectors such as pMT2PC (Kaufman et al. (1987), EMBO J. 6:187-195) for stable amplification/expression in mammalian cells. Vector DNA can be introduced into mammalian cells via conventional techniques such as calcium phosphate or calcium chloride co-precipitation. DEAE-dextran-mediated transfection, or electroporation. Suitable methods for transforming host cells can be found in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory press (1989)), and other laboratory textbooks.

Expression in procaryotes is most often carried out in E. coli with either fusion or non-fusion inducible expression vectors. Fusion vectors usually add a number of

NH

2 terminal amino acids to the expressed target gene. These NH 2 terminal amino acids often are referred to as a reporter group. Such reporter groups usually serve two purposes: 1) to increase the solubility of the target recombinant protein; and 2) to aid in the purification of the target recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the reporter group and the target recombinant protein to enable separation of the target recombinant protein from the reporter group subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition WO 98/18323 PCT/US97/19575 -33 sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Amrad Corp., Melbourne, Australia), pMAL (New England Biolabs, Beverly, MA) and pRITS (Pharmacia, Piscataway, NJ) which fuse glutathione S-transferase, maltose E binding protein, or protein A, respectively, to the target recombinant protein. A preferred reporter group is poly(His), which may be fused to the amino or carboxy terminus of the protein and which renders the recombinant fusion protein easily purifiable by metal chelate chromatography.

Inducible non-fusion expression vectors include pTrc (Amann et al., (1988) Gene 69:301-315) and pETI1 d (Studier et al., Gene Expression Technology: Methods in Enzvmology 185, Academic Press, San Diego, California (1990) 60-89). While target gene expression relies on host RNA polymerase transcription from the hybrid trp-lac fusion promoter in pTrc, expression of target genes inserted into pETI Id relies on transcription from the T7 gnl 0-lac 0 fusion promoter mediated by coexpressed viral RNA polymerase (T7 gnl). This viral polymerase is supplied by host strains BL21(DE3) or HMS 174(DE3) from a resident X prophage harboring a T7 gnl under the transcriptional control of the lacUV 5 promoter.

For example, a host cell transfected with a nucleic acid vector directing expression of a nucleotide sequence encoding an H. pylori polypeptide can be cultured under appropriate conditions to allow expression of the polypeptide to occur. The polypeptide may be secreted and isolated from a mixture of cells and medium containing the peptide. Alternatively, the polypeptide may be retained cytoplasmically and the cells harvested, lysed and the protein isolated. A cell culture includes host cells, media and other byproducts. Suitable media for cell culture are well known in the art.

Polypeptides of the invention can be isolated from cell culture medium, host cells, or both using techniques known in the art for purifying proteins including ion-exchange chromatography, gel filtration chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification with antibodies specific for such polypeptides.

Additionally, in many situations, polypeptides can be produced by chemical cleavage of a native protein tryptic digestion) and the cleavage products can then be purified by standard techniques.

In the case of membrane bound proteins, these can be isolated from a host cell by contacting a membrane-associated protein fraction with a detergent forming a solubilized complex, where the membrane-associated protein is no longer entirely embedded in the membrane fraction and is solubilized at least to an extent which allows it to be chromatographically isolated from the membrane fraction. Several different criteria are used for choosing a detergent suitable for solubilizing these complexes. For example, one property considered is the ability of the detergent to solubilize the H.

WO 98/18323 PCT/US97/19575 -34pylori protein within the membrane fraction at minimal denaturation of the membraneassociated protein allowing for the activity or functionality of the membrane-associated protein to return upon reconstitution of the protein. Another property considered when selecting the detergent is the critical micelle concentration (CMC) of the detergent in that the detergent of choice preferably has a high CMC value allowing for ease of removal after reconstitution. A third property considered when selecting a detergent is the hydrophobicity of the detergent. Typically, membrane-associated proteins are very hydrophobic and therefore detergents which are also hydrophobic, the triton series, would be useful for solubilizing the hydrophobic proteins. Another property important to a detergent can be the capability of the detergent to remove the H. pylori protein with minimal protein-protein interaction facilitating further purification. A fifth property of the detergent which should be considered is the charge of the detergent. For example, if it is desired to use ion exchange resins in the purification process then preferably detergent should be an uncharged detergent. Chromatographic techniques which can be used in the final purification step are known in the art and include hydrophobic interaction, lectin affinity, ion exchange, dye affinity and immunoaffinity.

One strategy to maximize recombinant H. pylori peptide expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein (Gottesman, Gene Expression Technology: Methods in Enzvmologyv 185, Academic Press, San Diego, California (1990) 119-128). Another strategy would be to alter the nucleic acid encoding an H. pylori peptide to be inserted into an expression vector so that the individual codons for each amino acid would be those preferentially utilized in highly expressed E. coli proteins (Wada et al., (1992) Nuc. Acids Res. 20:2111-2118). Such alteration of nucleic acids of the invention can be carried out by standard DNA synthesis techniques.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemically synthesizing polydeoxynucleotides are known, including solid-phase synthesis which, like peptide synthesis, has been fully automated in commercially available DNA synthesizers (See, Itakura et al. U.S.

Patent Nos. 4,401,796 and 4,373,071, incorporated by reference herein).

III. H. pylori Polypeptides This invention encompasses isolated H. pylori polypeptides encoded by the disclosed H pylori genomic sequences, including the polypeptides of the invention contained in the Sequence Listing. Polypeptides of the invention are preferably at least amino acid residues in length. Using the DNA sequence information provided herein, WO 98/18323 PCT/US97/19575 the amino acid sequences of the polypeptides encompassed by the invention can be deduced using methods well-known in the art. It will be understood that the sequence of an entire nucleic acid encoding an H pylori polypeptide can be isolated and identified based on an ORF that encodes only a fragment of the cognate protein-coding region.

This can be acheived, for example, by using the isolated nucleic acid encoding the ORF, or fragments thereof, to prime a polymerase chain reaction with genomic H. pylori DNA as template; this is followed by sequencing the amplified product.

The polypeptides of the invention can be isolated from wild-type or mutant H.

pylori cells or from heterologous organisms or cells (including, but not limited to, bacteria, yeast, insect, plant and mammalian cells) into which an H. pylori nucleic acid has been introduced and expressed. In addition, the polypeptides can be part of recombinant fusion proteins.

H. pylori polypeptides of the invention can be chemically synthesized using commercially automated procedures such as those referenced herein.

IV. Identification of Nucleic Acids Encoding Vaccine Components and Targets for Agents Effective Against H. pylori The disclosed H. pylori genome sequence includes segments that direct the synthesis of ribonucleic acids and polypeptides, as well as origins of replication, promoters, other types of regulatory sequences, and intergenic nucleic acids. The invention encompasses nucleic acids encoding immunogenic components of vaccines and targets for agents effective against H. pylori. Identification of said immunogenic components involved in the determination of the function of the disclosed sequences can be achieved using a variety of approaches. Non-limiting examples of these approaches are described briefly below.

Homology to known sequences: Computer-assisted comparison of the disclosed H. pylori sequences with previously reported sequences present in publicly available databases is useful for identifying functional H. pylori nucleic acid and polypeptide sequences. It will be understood that protein-coding sequences, for example, may be compared as a whole, and that a high degree of sequence homology between two proteins (such as, for example, >80-90%) at the amino acid level indicates that the two proteins also possess some degree of functional homology, such as, for example, among enzymes involved in metabolism, DNA synthesis, or cell wall synthesis, and proteins involved in transport, cell division, etc. In addition, many structural features of particular protein classes have been identified and correlate with specific consensus sequences, such as, for example, binding domains for nucleotides, DNA, metal ions, and other small molecules; sites for covalent modifications such as phosphorylation, WO 98/18323 PCT/US97/19575 -36acylation, and the like; sites of protein:protein interactions, etc. These consensus sequences may be quite short and thus may represent only a fraction of the entire protein-coding sequence. Identification of such a feature in an H. pylori sequence is therefore useful in determining the function of the encoded protein and identifying useful targets of antibacterial drugs.

Of particular relevance to the present invention are structural features that are common to secretory, transmembrane, and surface proteins, including secretion signal peptides and hydrophobic transmembrane domains. H. pylori proteins identified as containing putative signal sequences and/or transmembrane domains are useful as immunogenic components of vaccines.

Identification of essential genes: Nucleic acids that encode proteins essential for growth or viability of H. pylori are preferred drug targets. H. pylori genes can be tested for their biological relevance to the organism by examining the effect of deleting and/or disrupting the genes, by so-called gene "knockout", using techniques known to those skilled in the relevant art. In this manner, essential genes may be identified.

Strain-specific sequences: Because of the evolutionary relationship between different H. pylori strains, it is believed that the presently disclosed H. pylori sequences are useful for identifying, and/or discriminating between, previously known and new H.

pylori strains. It is believed that other H. pylori strains will exhibit at least sequence homology with the presently disclosed sequence. Systematic and routine analyses of DNA sequences derived from samples containing H. pylori strains, and comparison with the present sequence allows for the identification of sequences that can be used to discriminate between strains, as well as those that are common to all H. pylori strains. In one embodiment, the invention provides nucleic acids, including probes, and peptide and polypeptide sequences that discriminate between different strains of H.

pylori. Strain-specific components can also be identified functionally by their ability to elicit or react with antibodies that selectively recognize one or more H pylori strains.

In another embodiment, the invention provides nucleic acids, including probes, and peptide and polypeptide sequences that are common to all H. pylori strains but are not found in other bacterial species.

Specific Example: Determination Of Candidate Protein Antigens For Antibody And Vaccine Development The selection of candidate protein antigens for vaccine development can be derived from the nucleic acids encoding H. pylori polypeptides. First, the ORF's can be analyzed for homology to other known exported or membrane proteins and analyzed using the discriminant analysis described by Klein, et al. (Klein, Kanehsia, and WO 98/18323 PCT/US97/19575 -37- DeLisi, C. (1985) Biochimica et Biophysica Acta 815, 468-476) for predicting exported and membrane proteins.

Homology searches can be performed using the BLAST algorithm contained in the Wisconsin Sequence Analysis Package (Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711) to compare each predicted ORF amino acid sequence with all sequences found in the current GenBank, SWISS-PROT and PIR databases. BLAST searches for local alignments between the ORF and the databank sequences and reports a probability score which indicates the probability of finding this sequence by chance in the database. ORF's with significant homology (e.g.

probabilities lower than x 10- 6 that the homology is only due to random chance) to membrane or exported proteins represent protein antigens for vaccine development.

Possible functions can be provided to H. pylori genes based on sequence homology to genes cloned in other organisms.

Discriminant analysis (Klein, et al. supra) can be used to examine the ORF amino acid sequences. This algorithm uses the intrinsic information contained in the ORF amino acid sequence and compares it to information derived from the properties of known membrane and exported proteins. This comparison predicts which proteins will be exported, membrane associated or cytoplasmic. ORF amino acid sequences identified as exported or membrane associated by this algorithm are likely protein antigens for vaccine development.

Surface exposed outer membrane proteins are likely to represent the best antigens to provide a protective immune response against H. pylori. Among the algorithms that can be used to aid in prediction of these outer membrane proteins include the presence of an amphipathic beta-sheet region at their C-terminus. This region which has been detected in a large number of outer membrane proteins in Gram negative bacteria is often characterized by hydrophobic residues (Phe or Tyr) clustered at alternating positions from the C-terminus see Figure 5, block F; Figure 7, block E).

Importantly, these sequences have not been detected at the C-termini of periplasmic proteins, thus allowing preliminary distinction between these classes of proteins based on primary sequence data. This phenomenon has been reported previously by Struyve et al. Mol. Biol. 218:141-148, 1991).

Also illustrated in Figure 5 are additional amino acid sequence motifs found in many outer membrane proteins of H. pylori. The amino acid sequence alignment in Figure 5 depicts portions of the sequence of five H. pylori proteins (depicted in the single letter amino acid code) labeled with their amino acid Sequence ID Numbers and shown N-terminal to C-terminal, left to right. Five or six distinct blocks (labeled A through E or F) of similar amino acid residues are found including the distinctive WO 98/18323 PCTIUS97/19575 -38hydrophobic residues (Phe or Tyr; F or Y according to the single letter code for amino acid residues) frequently found at positions near the C-terminus of outer membrane proteins. The presence of several shared motifs clearly establishes the similarity between members of this group of proteins.

Additional amino acid alignments for four outer membrane proteins isolated from H. pylori are depicted in Figure 6.

Outer membrane proteins isolated from H. pylori frequently share additional motifs as depicted for two proteins in Figure 7 which also share the C-terminal hydrophobic residues, and as depicted for two proteins in Figure 8 which do not share the C-terminal hydrophobic residue motif but share a different C-terminal motif.

One skilled in the art would know that these shared sequence motifs are highly significant and establish a similarity among this group of proteins.

Infrequently it is not possible to distinguish between multiple possible nucleotides at a given position in the nucleic acid sequence. In those cases the ambiguities are denoted by an extended alphabet as follows: These are the official IUPAC-IUB single-letter base codes Code

G

A

T

C

R

Y

M

K

S

W

H

B

V

D

N

Base Description Guanine Adenine Thymine Cytosine Purine Pyrimidine Amino Ketone Strong interaction Weak interaction Not-G Not-A Not-T (not-U) Not-C Any (A or G) (C or T or U) (A or C) (G or T) (C or G) (A or T) (A or C or T) (C or G or T) (A or C or G) (A or G or T) (A or C or G or T) The amino acid translations of this invention account for the ambiguity in the nucleic acid sequence by translating the ambiguous codon as the letter In all cases, WO 98/18323 PCT/US97/19575 -39the permissible amino acid residues at a position are clear from an examination of the nucleic acid sequence based on the standard genetic code.

V. Production of Fragments and Analogs of H. pylori Nucleic Acids and Polvpeptides Based on the discovery of the H. pylori gene products of the invention provided in the Sequence Lsiting, one skilled in the art can alter the disclosed structure (of H.

pylori genes), by producing fragments or analogs, and test the newly produced structures for activity. Examples of techniques known to those skilled in the relevant art which allow the production and testing of fragments and analogs are discussed below.

These, or analogous methods can be used to make and screen libraries of polypeptides, libraries of random peptides or libraries of fragments or analogs of cellular proteins for the ability to bind H. pylori polypeptides. Such screens are useful for the identification of inhibitors of H. pylori.

Generation of Fragments Fragments of a protein can be produced in several ways, recombinantly, by proteolytic digestion, or by chemical synthesis. Internal or terminal fragments of a polypeptide can be generated by removing one or more nucleotides from one end (for a terminal fragment) or both ends (for an internal fragment) of a nucleic acid which encodes the polypeptide. Expression of the mutagenized DNA produces polypeptide fragments. Digestion with "end-nibbling" endonucleases can thus generate DNA's which encode an array of fragments. DNA's which encode fragments of a protein can also be generated by random shearing, restriction digestion or a combination of the above-discussed methods.

Fragments can also be chemically synthesized using techniques known in the art such as conventional Merrifield solid phase f-Moc or t-Boc chemistry. For example, peptides of the present invention may be arbitrarily divided into fragments of desired length with no overlap of the fragments, or divided into overlapping fragments of a desired length.

Alteration of Nucleic Acids and Polypeptides: Random Methods Amino acid sequence variants of a protein can be prepared by random mutagenesis of DNA which encodes a protein or a particular domain or region of a protein. Useful methods include PCR mutagenesis and saturation mutagenesis. A library of random amino acid sequence variants can also be generated by the synthesis of a set of degenerate oligonucleotide sequences. (Methods for screening proteins in a library of variants are elsewhere herein).

*t WO 98/18323 PCT/US97/19575 PCR Mutagenesis In PCR mutagenesis. reduced Taq polymerase fidelity is used to introduce random mutations into a cloned fragment of DNA (Leung et al., 1989, Technique 1:11- 15). The DNA region to be mutagenized is amplified using the polymerase chain reaction (PCR) under conditions that reduce the fidelity of DNA synthesis by Taq DNA polymerase, by using a dGTP/dATP ratio of five and adding Mn 2 to the PCR reaction. The pool of amplified DNA fragments are inserted into appropriate cloning vectors to provide random mutant libraries.

Saturation Mutagenesis Saturation mutagenesis allows for the rapid introduction of a large number of single base substitutions into cloned DNA fragments (Mayers et al., 1985, Science 229:242). This technique includes generation of mutations, by chemical treatment or irradiation of single-stranded DNA in vitro, and synthesis of a complimentary DNA strand. The mutation frequency can be modulated by modulating the severity of the treatment, and essentially all possible base substitutions can be obtained. Because this procedure does not involve a genetic selection for mutant fragments both neutral substitutions, as well as those that alter function, are obtained. The distribution of point mutations is not biased toward conserved sequence elements.

Degenerate Oligonucleotides A library of homologs can also be generated from a set of degenerate oligonucleotide sequences. Chemical synthesis of a degenerate sequences can be carried out in an automatic DNA synthesizer, and the synthetic genes then ligated into an appropriate expression vector. The synthesis of degenerate oligonucleotides is known in the art (see for example, Narang, SA (1983) Tetrahedron 39:3; Itakura et al. (1981) Recombinant DNA, Proc 3rd Cleveland Sympos. Macromolecules, ed. AG Walton, Amsterdam: Elsevier pp 2 7 3 -289; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakura et al. (1984) Science 198:1.056; Ike et al. (1983) Nucleic Acid Res. 11:477. Such techniques have been employed in the directed evolution of other proteins (see, for example, Scott et al. (1990) Science 249:386-390; Roberts et al. (1992) PNAS 89:2429- 2433; Devlin et al. (1990) Science 249: 404-406; Cwirla et al. (1990) PNAS 87: 6378- 6382; as well as U.S. Patents Nos. 5,223,409, 5,198,346, and 5,096,815).

WO 98/18323 PCT/US97/19575 -41 Alteration of Nucleic Acids and Polypeptides: Methods for Directed Mutagenesis Non-random or directed, mutagenesis techniques can be used to provide specific sequences or mutations in specific regions. These techniques can be used to create variants which include, deletions, insertions, or substitutions, of residues of the known amino acid sequence of a protein. The sites for mutation can be modified individually or in series, by substituting first with conserved amino acids and then with more radical choices depending upon results achieved, deleting the target residue, or inserting residues of the same or a different class adjacent to the located site, or combinations of options 1-3.

Alanine Scanning Mutagenesis Alanine scanning mutagenesis is a useful method for identification of certain residues or regions of the desired protein that are preferred locations or domains for mutagenesis, Cunningham and Wells (Science 244:1081-1085, 1989). In alanine scanning, a residue or group of target residues are identified charged residues such as Arg, Asp, His, Lys, and Glu) and replaced by a neutral or negatively charged amino acid (most preferably alanine or polyalanine). Replacement of an amino acid can affect the interaction of the amino acids with the surrounding aqueous environment in or outside the cell. Those domains demonstrating functional sensitivity to the substitutions are then refined by introducing further or other variants at or for the sites of substitution.

Thus, while the site for introducing an amino acid sequence variation is predetermined, the nature of the mutation per se need not be predetermined. For example, to optimize the performance of a mutation at a given site, alanine scanning or random mutagenesis may be conducted at the target codon or region and the expressed desired protein subunit variants are screened for the optimal combination of desired activity.

Oligonucleotide-Mediated Mutagenesis Oligonucleotide-mediated mutagenesis is a useful method for preparing substitution, deletion, and insertion variants of DNA, see, Adelman et al., (DNA 2:183, 1983). Briefly, the desired DNA is altered by hybridizing an oligonucleotide encoding a mutation to a DNA template, where the template is the single-stranded form of a plasmid or bacteriophage containing the unaltered or native DNA sequence of the desired protein. After hybridization, a DNA polymerase is used to synthesize an entire second complementary strand of the template that will thus incorporate the oligonucleotide primer, and will code for the selected alteration in the desired protein DNA. Generally, oligonucleotides of at least 25 nucleotides in length are used. An optimal oligonucleotide will have 12 to 15 nucleotides that are completely WO 98/18323 PCT/US97/19575 -42complementary to the template on either side of the nucleotide(s) coding for the mutation. This ensures that the oligonucleotide will hybridize properly to the singlestranded DNA template molecule. The oligonucleotides are readily synthesized using techniques known in the art such as that described by Crea et al. (Proc. Natl. Acad. Sci.

USA, 75: 5765[1978]).

Cassette Mutagenesis Another method for preparing variants, cassette mutagenesis, is based on the technique described by Wells et al. (Gene, 34:315[1985]). The starting material is a plasmid (or other vector) which includes the protein subunit DNA to be mutated. The codon(s) in the protein subunit DNA to be mutated are identified. There must be a unique restriction endonuclease site on each side of the identified mutation site(s). If no such restriction sites exist, they may be generated using the above-described oligonucleotide-mediated mutagenesis method to introduce them at appropriate locations in the desired protein subunit DNA. After the restriction sites have been introduced into the plasmid, the plasmid is cut at these sites to linearize it. A double-stranded oligonucleotide encoding the sequence of the DNA between the restriction sites but containing the desired mutation(s) is synthesized using standard procedures. The two strands are synthesized separately and then hybridized together using standard techniques. This double-stranded oligonucleotide is referred to as the cassette. This cassette is designed to have 3' and 5' ends that are comparable with the ends of the linearized plasmid, such that it can be directly ligated to the plasmid. This plasmid now contains the mutated desired protein subunit DNA sequence.

Combinatorial Mutagenesis Combinatorial mutagenesis can also be used to generate mutants (Ladner et al., WO 88/06630). In this method, the amino acid sequences for a group of homologs or other related proteins are aligned, preferably to promote the highest homology possible.

All of the amino acids which appear at a given position of the aligned sequences can be selected to create a degenerate set of combinatorial sequences. The variegated library of variants is generated by combinatorial mutagenesis at the nucleic acid level, and is encoded by a variegated gene library. For example, a mixture of synthetic oligonucleotides can be enzymatically ligated into gene sequences such that the degenerate set of potential sequences are expressible as individual peptides, or alternatively, as a set of larger fusion proteins containing the set of degenerate sequences.

WO 98/18323 PCT/US97/19575 -43- Other Modifications of H. pylori Nucleic Acids and Polvpeptides It is possible to modify the structure of an H. pylori polypeptide for such purposes as increasing solubility, enhancing stability shelf life ex vivo and resistance to proteolytic degradation in vivo). A modified H. pylori protein or peptide can be produced in which the amino acid sequence has been altered, such as by amino acid substitution, deletion, or addition as described herein.

An H. pylori peptide can also be modified by substitution of cysteine residues preferably with alanine, serine, threonine, leucine or glutamic acid residues to minimize dimerization via disulfide linkages. In addition, amino acid side chains of fragments of the protein of the invention can be chemically modified. Another modification is cyclization of the peptide.

In order to enhance stability and/or reactivity, an H. pylori polypeptide can be modified to incorporate one or more polymorphisms in the amino acid sequence of the protein resulting from any natural allelic variation. Additionally, D-amino acids, nonnatural amino acids, or non-amino acid analogs can be substituted or added to produce a modified protein within the scope of this invention. Furthermore, an H. pylori polypeptide can be modified using polyethylene glycol (PEG) according to the method of A. Sehon and co-workers (Wie et al., supra) to produce a protein conjugated with PEG. In addition, PEG can be added during chemical synthesis of the protein. Other modifications ofH. pylori proteins include reduction/alkylation (Tarr, Methods of Protein Microcharacterization, J. E. Silver ed., Humana Press, Clifton NJ 155-194 (1986)); acylation (Tarr, supra); chemical coupling to an appropriate carrier (Mishell and Shiigi, eds, Selected Methods in Cellular Immunology, WH Freeman. San Francisco, CA (1980), U.S. Patent 4,939,239; or mild formalin treatment (Marsh, (1971) Int. Arch. of Allergy andAppl. Immunol., 41: 199 215).

To facilitate purification and potentially increase solubility of an H. pylori protein or peptide, it is possible to add an amino acid fusion moiety to the peptide backbone. For example, hexa-histidine can be added to the protein for purification by immobilized metal ion affinity chromatography (Hochuli, E. et al., (1988) Bio/Technology, 6: 1321 1325). In addition, to facilitate isolation of peptides free of irrelevant sequences, specific endoprotease cleavage sites can be introduced between the sequences of the fusion moiety and the peptide.

To potentially aid proper antigen processing of epitopes within an H. pylori polypeptide, canonical protease sensitive sites can be engineered between regions, each comprising at least one epitope via recombinant or synthetic methods. For example, charged amino acid pairs, such as KK or RR, can be introduced between regions within a protein or fragment during recombinant construction thereof. The resulting peptide WO 98/18323 PCT/US97/19575 -44can be rendered sensitive to cleavage by cathepsin and/or other trypsin-like enzymes which would generate portions of the protein containing one or more epitopes. In addition, such charged amino acid residues can result in an increase in the solubility of the peptide.

Primary Methods for Screening Polypeptides and Analogs Various techniques are known in the art for screening generated mutant gene products. Techniques for screening large gene libraries often include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the genes under conditions in which detection of a desired activity, in this case, binding to H. pylori polypeptide or an interacting protein, facilitates relatively easy isolation of the vector encoding the gene whose product was detected. Each of the techniques described below is amenable to high through-put analysis for screening large numbers of sequences created, by random mutagenesis techniques.

Two Hybrid Systems Two hybrid assays such as the system described above (as with the other screening methods described herein), can be used to identify polypeptides, e.g., fragments or analogs of a naturally-occurring H. pylori polypeptide, of cellular proteins, or of randomly generated polypeptides which bind to an H. pylori protein.

(The H. pylori domain is used as the bait protein and the library of variants are expressed as fish fusion proteins.) In an analogous fashion, a two hybrid assay (as with the other screening methods described herein), can be used to find polypeptides which bind a H.

pylori polypeptide.

Display Libraries In one approach to screening assays, the candidate peptides are displayed on the surface of a cell or viral particle, and the ability of particular cells or viral particles to bind an appropriate receptor protein via the displayed product is detected in a "panning assay". For example, the gene library can be cloned into the gene for a surface membrane protein of a bacterial cell, and the resulting fusion protein detected by panning (Ladner et al., WO 88/06630; Fuchs et al. (1991) Bio/Technology 9:1370-1371; and Goward et al. (1992) TIBS 18:136-140). In a similar fashion, a detectably labeled ligand can be used to score for potentially functional peptide homologs. Fluorescently labeled ligands, receptors. can be used to detect homologs which retain ligandbinding activity. The use of fluorescently labeled ligands, allows cells to be visually WO 98/18323 PCT/US97/19575 inspected and separated under a fluorescence microscope, or, where the morphology of the cell permits, to be separated by a fluorescence-activated cell sorter.

A gene library can be expressed as a fusion protein on the surface of a viral particle. For instance, in the filamentous phage system, foreign peptide sequences can be expressed on the surface of infectious phage, thereby conferring two significant benefits. First, since these phage can be applied to affinity matrices at concentrations well over 1013 phage per milliliter, a large number of phage can be screened at one time.

Second, since each infectious phage displays a gene product on its surface, if a particular phage is recovered from an affinity matrix in low yield, the phage can be amplified by another round of infection. The group of almost identical E. coli filamentous phages M13, fd., and fl are most often used in phage display libraries. Either of the phage gill or gVIII coat proteins can be used to generate fusion proteins without disrupting the ultimate packaging of the viral particle. Foreign epitopes can be expressed at the NH 2 terminal end of pIIl and phage bearing such epitopes recovered from a large excess of phage lacking this epitope (Ladner et al. PCT publication WO 90/02909; Garrard et al., PCT publication WO 92/09690; Marks et al. (1992) J. Biol. Chem. 267:16007-16010; Griffiths et al. (1993) EMBO J 12:725-734; Clackson et al. (1991) Nature 352:624-628; and Barbas et al. (1992) PNAS 89:4457-4461).

A common approach uses the maltose receptor of E. coli (the outer membrane protein, LamB) as a peptide fusion partner (Charbit et al. (1986) EMBO 5, 3029-3037).

Oligonucleotides have been inserted into plasmids encoding the LamB gene to produce peptides fused into one of the extracellular loops of the protein. These peptides are available for binding to ligands. to antibodies, and can elicit an immune response when the cells are administered to animals. Other cell surface proteins, OmpA (Schorr et al. (1991) Vaccines 91, pp. 387-392), PhoE (Agterberg, et al. (1990) Gene 88, 37-45), and PAL (Fuchs et al. (1991) Bio/Tech 9, 1369-1372), as well as large bacterial surface structures have served as vehicles for peptide display. Peptides can be fused to pilin, a protein which polymerizes to form the pilus-a conduit for interbacterial exchange of genetic information (Thiry et al. (1989) Appl. Environ. Microbiol. 55, 984-993).

Because of its role in interacting with other cells, the pilus provides a useful support for the presentation of peptides to the extracellular environment. Another large surface structure used for peptide display is the bacterial motive organ, the flagellum. Fusion of peptides to the subunit protein flagellin offers a dense array of many peptide copies on the host cells (Kuwajima et al. (1988) Bio/Tech. 6, 1080-1083). Surface proteins of other bacterial species have also served as peptide fusion partners. Examples include the Staphylococcus protein A and the outer membrane IgA protease of Neisseria (Hansson WO 98/18323 PCT/US97/19575 -46et al. (1992) J. Bacteriol. 174, 4239-4245 and Klauser et al. (1990) EMBOJ. 9, 1991- 1999).

In the filamentous phage systems and the LamB system described above, the physical link between the peptide and its encoding DNA occurs by the containment of the DNA within a particle (cell or phage) that carries the peptide on its surface.

Capturing the peptide captures the particle and the DNA within. An alternative scheme uses the DNA-binding protein Lad to form a link between peptide and DNA (Cull et al.

(1992) PNAS USA 89:1865-1869). This system uses a plasmid containing the LacI gene with an oligonucleotide cloning site at its 3'-end. Under the controlled induction by arabinose, a LacI-peptide fusion protein is.produced. This fusion retains the natural ability of LacI to bind to a short DNA sequence known as LacO operator (LacO). By installing two copies of LacO on the expression plasmid, the LacI-peptide fusion binds tightly to the plasmid that encoded it. Because the plasmids in each cell contain only a single oligonucleotide sequence and each cell expresses only a single peptide sequence, the peptides become specifically and stably associated with the DNA sequence that directed its synthesis. The cells of the library are gently lysed and the peptide-DNA complexes are exposed to a matrix of immobilized receptor to recover the complexes containing active peptides. The associated plasmid DNA is then reintroduced into cells for amplification and DNA sequencing to determine the identity of the peptide ligands.

As a demonstration of the practical utility of the method, a large random library of dodecapeptides was made and selected on a monoclonal antibody raised against the opioid peptide dynorphin B. A cohort of peptides was recovered, all related by a consensus sequence corresponding to a six-residue portion of dynorphin B. (Cull et al.

(1992) Proc. Natl. Acad. Sci. U.S.A. 89-1869) This scheme, sometimes referred to.as peptides-on-plasmids, differs in two important ways from the phage display methods. First, the peptides are attached to the C-terminus of the fusion protein, resulting in the display of the library members as peptides having free carboxy termini. Both of the filamentous phage coat proteins, pill and pVIII, are anchored to the phage through their C-termini, and the guest peptides are placed into the outward-extending N-terminal domains. In some designs, the phagedisplayed peptides are presented right at the amino terminus of the fusion protein.

(Cwirla, et al. (1990) Proc. Natl. Acad. Sci. US.A. 87, 6378-6382) A second difference is the set of biological biases affecting the population of peptides actually present in the libraries. The LacI fusion molecules are confined to the cytoplasm of the host cells.

The phage coat fusions are exposed briefly to the cytoplasm during translation but are rapidly secreted through the inner membrane into the periplasmic compartment, remaining anchored in the membrane by their C-terminal hydrophobic domains, with the WO 98/18323 PCT/US97/19575 -47- N-termini, containing the peptides, protruding into the periplasm while awaiting assembly into phage particles. The peptides in the LacI and phage libraries may differ significantly as a result of their exposure to different proteolytic activities. The phage coat proteins require transport across the inner membrane and signal peptidase processing as a prelude to incorporation into phage. Certain peptides exert a deleterious effect on these processes and are underrepresented in the libraries (Gallop et al. (1994) J.

Med. Chem. 37(9):1233-1251). These particular biases are not a factor in the LacI display system.

The number of small peptides available in recombinant random libraries is enormous. Libraries of 107-109 independent clones are routinely prepared. Libraries as large as 1011 recombinants have been created, but this size approaches the practical limit for clone libraries. This limitation in library size occurs at the step of transforming the DNA containing randomized segments into the host bacterial cells. To circumvent this limitation, an in vitro system based on the display of nascent peptides in polysome complexes has recently been developed. This display library method has the potential of producing libraries 3-6 orders of magnitude larger than the currently available phage/phagemid or plasmid libraries. Furthermore, the construction of the libraries, expression of the peptides, and screening, is done in an entirely cell-free format.

In one application of this method (Gallop et al. (1994) J. Med. Chem.

37(9):1233-1251), a molecular DNA library encoding 1012 decapeptides was constructed and the library expressed in an E. coli S30 in vitro coupled transcription/translation system. Conditions were chosen to stall the ribosomes on the mRNA. causing the accumulation of a substantial proportion of the RNA in polysomes and yielding complexes containing nascent peptides still linked to their encoding RNA.

The polysomes are sufficiently robust to be affinity purified on immobilized receptors in much the same way as the more conventional recombinant peptide display libraries are screened. RNA from the bound complexes is recovered, converted to cDNA, and amplified by PCR to produce a template for the next round of synthesis and screening.

The polysome display method can be coupled to the phage display system. Following several rounds of screening, cDNA from the enriched pool of polysomes was cloned into a phagemid vector. This vector serves as both a peptide expression vector, displaying peptides fused to the coat proteins, and as a DNA sequencing vector for peptide identification. By expressing the polysome-derived peptides on phage, one can either continue the affinity selection procedure in this format or assay the peptides on individual clones for binding activity in a phage ELISA, or for binding specificity in a completion phage ELISA (Barret, et al. (1992) Anal. Biochem 204,357-364). To WO 98/18323 PCT/US97/19575 -48identify the sequences of the active peptides one sequences the DNA produced by the phagemid host.

Secondary Screening of Polypeptides and Analogs The high through-put assays described above can be followed by secondary screens in order to identify further biological activities which will, allow one skilled in the art to differentiate agonists from antagonists. The type of a secondary screen used will depend on the desired activity that needs to be tested. For example, an assay can be developed in which the ability to inhibit an interaction between a protein of interest and its respective ligand can be used to identify antagonists from a group of peptide fragments isolated though one of the primary screens described above.

Therefore,.methods for generating fragments and analogs and testing them for activity are known in the art. Once the core sequence of interest is identified, it is routine for one skilled in the art to obtain analogs and fragments.

Peptide Mimetics of H. pylori Polypeptides The invention also provides for reduction of the protein binding domains of the subject H. pylori polypeptides to generate mimetics, e.g. peptide or non-peptide agents.

The peptide mimetics are able to disrupt binding of a polypeptide to its counter ligand, in the case of an H. pylori polypeptide binding to a naturally occurring ligand. The critical residues of a subject H. pylori polypeptide which are involved in molecular recognition of a polypeptide can be determined and used to generate H. pylori-derived peptidomimetics which competitively or noncompetitively inhibit binding of the H.

pylori polypeptide with an interacting polypeptide (see. for example, European patent applications EP-412,762A and EP-B31,080A).

For example, scanning mutagenesis can be used to map the amino acid residues of a particular H. pylori polypeptide involved in binding an interacting polypeptide, peptidomimetic compounds diazepine or isoquinoline derivatives) can be generated which mimic those residues in binding to an interacting polypeptide, and which therefore can inhibit binding of an H pylori polypeptide to an interacting polypeptide and thereby interfere with the function of H pylori polypeptide. For instance, nonhydrolyzable peptide analogs of such residues can be generated using benzodiazepine see Freidinger et al. in Peptides: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), azepine see Huffman et al. in Peptides: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted gama lactam rings (Garvey et al. in Peptides: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), keto- WO 98/18323 PCT/US97/19575 -49methylene pseudopeptides (Ewenson et al. (1986)J Med Chem 29:295; and Ewenson et al. in Peptides: Structure and Function (Proceedings of the 9th American Peptide Symposium) Pierce Chemical Co. Rockland, IL, 1985), p-tum dipeptide cores (Nagai et al. (1985) Tetrahedron Lett 26:647; and Sato et al. (1986) J Chem Soc Perkin Trans 1:1231), and P-aminoalcohols (Gordon et al. (1985) Biochem Biophys Res Commun126:419; and Dann et al. (1986) Biochem Biophys Res Commun 134:71).

VI. Vaccine Formulations for H. pylori Nucleic Acids and Polvpeptides This invention also features vaccine compositions or formulations (used interchangeably herein) for protection against infection by H. pylori or for treatment of H pylori infection. As used herein, the term "treatment of H pylori infection" refers to therapeutic treatment of an existing or established H. pylori infection. The terms "protection against H. pylori infection" or "prophylactic treatment" refer to the use of H.

pylori vaccine formulation for reducing the risk of or preventing an infection in a subject at risk for H. pylori infection. In one embodiment, the vaccine compositions contain one or more immunogenic components, such as a surface protein, from H pylori, or portion thereof, and a pharmaceutically acceptable carrier. For example, in one embodiment, the vaccine formulations of the invention contain at least one or combination of H. pylori polypeptides or fragments thereof, from same or different H. pylori antigens. Nucleic acids and H. pylori polypeptides for use in the vaccine formulations of the invention include the nucleic acids and polypeptides set forth in the Sequence Listing, preferably those H. pylori nucleic acids that encode surface proteins and surface proteins or fragments thereof. For example, a preferred nucleic acid and H. pylori polypeptide for use in a vaccine composition of the invention is selected from the group of nucleic acids which encode cell envelope proteins and H. pylori cell envelope proteins as set forth in Table 1. However, any nucleic acid encoding an immunogenic H. pylori protein and H.

pylori polypetide, or portion thereof, can be used in the present invention. These vaccines have therapeutic and/or prophylactic utilities.

One aspect of the invention provides a vaccine composition for protection against infection by H. pylori which contains at least one immunogenic fragment of an H pylori protein and a pharmaceutically acceptable carrier. Preferred fragments include peptides of at least about 10 amino acid residues in length, preferably about 10-20 amino acid residues in length, and more preferably about 12-16 amino acid residues in length.

Immunogenic components of the invention can be obtained, for example, by screening polypeptides recombinantly produced from the corresponding fragment of the nucleic acid encoding the full-length H pylori protein. In addition, fragments can be WO 98/18323 PCTIUS97/19575 chemically synthesized using techniques known in the art such as conventional Merrifield solid phase f-Moc or t-Boc chemistry.

In one embodiment, immunogenic components are identified by the ability of the peptide to stimulate T cells. Peptides which stimulate T cells, as determined by, for example, T cell proliferation or cytokine secretion are defined herein as comprising at least one T cell epitope. T cell epitopes are believed to be involved in initiation and perpetuation of the immune response to the protein allergen which is responsible for the clinical symptoms of allergy. These T cell epitopes are thought to trigger early events at the level of the T helper cell by binding to an appropriate HLA molecule on the surface of an antigen presenting cell, thereby stimulating the T cell subpopulation with the relevant T cell receptor for the epitope. These events lead to T cell proliferation, lymphokine secretion, local inflammatory reactions, recruitment of additional immune cells to the site of antigen/T cell interaction, and activation of the B cell cascade, leading to the production of antibodies. A T cell epitope is the basic element, or smallest unit of recognition by a T cell receptor, where the epitope comprises amino acids essential to receptor recognition approximately 6 or 7 amino acid residues). Amino acid sequences which mimic those of the T cell epitopes are within the scope of this invention.

In another embodiment, immunogenic components of the invention are identified through genomic vaccination. The basic protocol is based on the idea that expression libraries consisting of all or parts of a pathogen genome, an H. pylori genome, can confer protection when used to genetically immunize a host. This expression library immunization (ELI) is analogous to expression cloning and involves reducing a genomic expression library of a pathogen, H. pylori, into plasmids that can act as genetic vaccines. The plasmids can also be designed to encode genetic adjuvants which can dramatically stimulate the humoral response. These genetic adjuvants can be introduced at remote sites and act as well extracelluraly as intracellularly.

This is a new approach to vaccine production that has many of the advantages of live/attenuated pathogens but no risk of infection. An expression library of pathogen DNA is used to immunize a host thereby producing the effects of antigen presentation of a live vaccine without the risk. For example, in the present invention, random fragments from the H. pylori genome or from cosmid or plasmid clones, as well as PCR products from genes identified by genomic sequencing, can be used to immunize a host. The feasibility of this approach has been demonstrated with Mycoplasma pulmonis (Barry et al., Nature 377:632-635, 1995), where even partial expression libraries of Mycoplasma pulmonis, a natural pathogen in rodents, provided protection against challenge from the pathogen.

WO 98/18323 PCT/US97/19575 -51- ELI is a technique that allows for production of a non-infectious multipartite vaccine, even when little is known about pathogen's biology, because ELI uses the immune system to screen candidate genes. Once isolated, these genes can be used as genetic vaccines or for development of recombinant protein vaccines. Thus, ELI allows for production of vaccines in a systemaitic, largely mechanized fashion.

Screening immunogenic components can be accomplished using one or more of several different assays. For example, in vitro, peptide T cell stimulatory activity is assayed by contacting a peptide known or suspected of being immunogenic with an antigen presenting cell which presents appropriate MHC molecules in a T cell culture.

Presentation of an immunogenic H. pylori peptide in association with appropriate MHC molecules to T cells in conjunction with the necessary costimulation has the effect of transmitting a signal to the T cell that induces the production of increased levels of cytokines, particularly of interleukin-2 and interleukin-4. The culture supemrnatant can be obtained and assayed for interleukin-2 or other known cytokines. For example, any one of several conventional assays for interleukin-2 can be employed, such as the assay described in Proc. Natl. Acad Sci USA, 86: 1333 (1989) the pertinent portions of which are incorporated herein by reference. A kit for an assay for the production of interferon is also available from Genzyme Corporation (Cambridge, MA).

Alternatively, a common assay for T cell proliferation entails measuring tritiated thymidine incorporation. The proliferation of T cells can be measured in vitro by determining the amount of 3 H-labeled thymidine incorporated into the replicating DNA of cultured cells. Therefore, the rate of DNA synthesis and, in turn, the rate of cell division can be quantified.

Vaccine compositions or formulations of the invention containing one or more immunogenic components H. pylori polypeptide or fragment thereof or nucleic acid encoding an H. pylori polypeptide or fragment thereof) preferably include a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable pharmaceutically acceptable carriers include, for example, one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof. Pharmaceutically acceptable carriers may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the H. pylori nucleic acid or polypeptide. For vaccine formulations of the invention containing H pylori polypeptides, the polypeptide is preferably coadministered with a suitable adjuvant and/or a delivery system described herein.

WO 98/18323 PCT/US97/19575 -52- It will be apparent to those of skill in the art that the therapeutically effective amount of DNA or protein of this invention will depend, inter alia, upon the administration schedule, the unit dose of an H pylori nucleic acid or polypeptide administered, whether the protein or nucleic acid is administered in combination with other therapeutic agents, the immune status and health of the patient, and the therapeutic activity of the particular protein or nucleic acid.

Vaccine formulations are conventionally administered parenterally, by injection, either subcutaneously or intramuscularly. Methods for intramuscular immunization are described by Wolff et al. (1990) Science 247: 1465-1468 and by Sedegah et al. (1994) Immunology 91: 9866-9870. Other modes of administration include oral and pulmonary formulations, suppositories, and transdermal applications.

Oral immunization is preferred over parenteral methods for inducing protection against infection by H. pylori. Czinn et. al. (1993) Vaccine 11: 637-642. Oral formulations include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like.

In one embodiment, the vaccine formulation includes, as a pharmaceutically acceptable carrier, an adjuvant. Examples of the suitable adjuvants for use in the vaccine formulations of the invention include, but are not limited, to aluminum hydroxide; N-acetyl-muramyl--L-threonyl-D-isoglutamine (thr-MDP); N-acetyl-normuramyl-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-MDP); Nacetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-( '-2'-dipalmitoyl-sn-glycero-3hydroxyphos-phoryloxy)-ethylamine (CGP 19835A, referred to a MTP-PE); RIBI, which contains three components from bacteria; monophosphoryl lipid A; trehalose dimycoloate; cell wall skeleton (MPL TDM CWS) in a 2% squalene/Tween emulsion; and cholera toxin. Others which may be used are non-toxic derivatives of cholera toxin, including its B subunit, and/or conjugates or genetically engineered fusions of the H pylori polypeptide with cholera toxin or its B subunit, procholeragenoid, fungal polysaccharides, including schizophyllan, muramyl dipeptide, muramyl dipeptide derivatives, phorbol esters, labile toxin of E. coli, non-H pylori bacterial lysates, block polymers or saponins.

In another embodiment, the vaccine formulation includes, as a pharmaceutically acceptable carrier, a delivery system. Suitable delivery systems for use in the vaccine formulations of the invention include biodegradable microcapsules or immunostimulating complexes (ISCOMs), cochleates, or liposomes, genetically engineered attenuated live vectors such as viruses or bacteria, and recombinant (chimeric) virus-like WO 98/18323 PCT/US97/19575 53 particles, bluetongue. In another embodiment of the invention, the vaccine formulation includes both a delivery system and an adjuvant.

Delivery systems in humans may include enteric release capsules protecting the antigen from the acidic environment of the stomach, and including H pylori polypeptide in an insoluble form as fusion proteins. Suitable carriers for the vaccines of the invention are enteric coated capsules and polylactide-glycolide microspheres. Suitable diluents are 0.2 N NaHCO3 and/or saline.

Vaccines of the invention can be administered as a primary prophylactic agent in adults or in children, as a secondary prevention, after successful eradication of H. pylori in an infected host, or as a therapeutic agent in the aim to induce an immune response in a susceptible host to prevent infection by H pylori. The vaccines of the invention are administered in amounts readily determined by persons of ordinary skill in the art.

Thus, for adults a suitable dosage will be in the range of 10 plg to 10 g, preferably 10 pg to 100 mg, for example 50 pg to 50 mg. A suitable dosage for adults will also be in the range of 5 pg to 500 mg. Similar dosage ranges will be applicable for children.

The amount of adjuvant employed will depend on the type of adjuvant used. For example, when the mucosal adjuvant is cholera toxin, it is suitably used in an amount of pg to 50 pg, for example 10 pg to 35 p.g. When used in the form of microcapsules, the amount used will depend on the amount employed in the matrix of the microcapsule to achieve the desired dosage. The determination of this amount is within the skill of a person of ordinary skill in the art.

Those skilled in the art will recognize that the optimal dose may be more or less depending upon the patient's body weight, disease, the route of administration, and other factors. Those skilled in the art will also recognize that appropriate dosage levels can be obtained based on results with known oral vaccines such as, for example, a vaccine based on an E. coli lysate (6 mg dose daily up to total of 540 mg) and with an enterotoxigenic E. coli purified antigen (4 doses of 1 mg) (Schulman et al., J. Urol.

150:917-921 (1993)); Boedecker et al., American Gastroenterological Assoc. 999:A-222 (1993)). The number of doses will depend upon the disease, the formulation, and efficacy data from clinical trials. Without intending any limitation as to the course of treatment, the treatment can be administered over 3 to 8 doses for a primary immunization schedule over 1 month (Boedeker, American Gastroenterological Assoc.

888:A-222 (1993)).

In a preferred embodiment, a vaccine composition of the invention can be based on a killed whole E. coli preparation with an immunogenic fragment of an H. pylori protein of the invention expressed on its surface or it can be based on an E. coli lysate, wherein the killed E. coli acts as a carrier or an adjuvant.

WO 98/18323 PCT/US97/19575 -54- It will be apparent to those skilled in the art that some of the vaccine compositions of the invention are useful only for preventing H. pylori infection, some are useful only for treating H. pylori infection, and some are useful for both preventing and treating H. pylori infection. In a preferred embodiment, the vaccine composition of the invention provides protection against H. pylori infection by stimulating humoral and/or cell-mediated immunity against H. pylori. It should be understood that amelioration of any of the symptoms of H. pylori infection is a desirable clinical goal, including a lessening of the dosage of medication used to treat H. pylori-caused disease, or an increase in the production of antibodies in the serum or mucous of patients.

VII. Antibodies Reactive With H. p'lori Polypeptides The invention also includes antibodies specifically reactive with the subject H.

pylori polypeptide. Anti-protein/anti-peptide antisera or monoclonal antibodies can be made by standard protocols (See, for example, Antibodies. A Laboratory Manual ed. by Harlow and Lane (Cold Spring Harbor Press: 1988)). A mammal such as a mouse, a hamster or rabbit can be immunized with an immunogenic form of the peptide.

Techniques for conferring immunogenicity on a protein or peptide include conjugation to carriers or other techniques well known in the art. An immunogenic portion of the subject H. pylori polypeptide can be administered in the presence of adjuvant. The progress of immunization can be monitored by detection of antibody titers in plasma or serum. Standard ELISA or other immunoassays can be used with the immunogen as antigen to assess the levels of antibodies.

In a preferred embodiment, the subject antibodies are immunospecific for antigenic determinants of the H. pylori polypeptides of the invention, e.g. antigenic determinants of a polypeptide of the invention contained in the Sequence Listing, or a closely related human or non-human mammalian homolog 90% homologous, more preferably at least 95% homologous). In yet a further preferred embodiment of the invention, the anti-H, pylori antibodies do not substantially cross react react specifically) with a protein which is for example, less than 80% percent homologous to a sequence of the invention contained in the Sequence Listing. By "not substantially cross react", it is meant that the antibody has a binding affinity for a non-homologous protein which is less than 10 percent, more preferably less than 5 percent, and even more preferably less than 1 percent, of the binding affinity for a protein of the invention contained in the Sequence Listing. In a most preferred embodiment, there is no crossreactivity between bacterial and mammalian antigens.

The term antibody as used herein is intended to include fragments thereof which are also specifically reactive with H pylori polypeptides. Antibodies can be fragmented WO 98/18323 PCT/US97/19575 using conventional techniques and the fragments screened for utility in the same manner as described above for whole antibodies. For example, F(ab') 2 fragments can be generated by treating antibody with pepsin. The resulting F(ab') 2 fragment can be treated to reduce disulfide bridges to produce Fab' fragments. The antibody of the invention is further intended to include bispecific and chimeric molecules having an anti-H. pylori portion.

Both monoclonal and polyclonal antibodies (Ab) directed against H. pylori polypeptides or H. pylori polypeptide variants, and antibody fragments such as Fab' and F(ab')2, can be used to block the action of H. pylori polypeptide and allow the study of the role of a particular H. pylori polypeptide of the invention in aberrant or unwanted intracellular signaling, as well as the normal cellular function of the H. pylori and by microinjection of anti-H. pylori polypeptide antibodies of the present invention.

Antibodies which specifically bind H pylori epitopes can also be used in immunohistochemical staining of tissue samples in order to evaluate the abundance and pattern of expression of H. pylori antigens. Anti H pylori polypeptide antibodies can be used diagnostically in immuno-precipitation and immuno-blotting to detect and evaluate H. pylori levels in tissue or bodily fluid as part of a clinical testing procedure. Likewise, the ability to monitor H. pylori polypeptide levels in an individual can allow determination of the efficacy of a given treatment regimen for an individual afflicted with such a disorder. The level of an H pylori polypeptide can be measured in cells found in bodily fluid, such as in urine samples or can be measured in tissue, such as produced by gastric biopsy. Diagnostic assays using anti-H pylori antibodies can include, for example, immunoassays designed to aid in early diagnosis of H pylori infections. The present invention can also be used as a method of detecting antibodies contained in samples from individuals infected by this bacterium using specific H. pylori antigens.

Another application of anti-H. pylori polypeptide antibodies of the invention is in the immunological screening of cDNA libraries constructed in expression vectors such as kgtl 1, Xgtl8-23, XZAP, and .ORF8. Messenger libraries of this type, having coding sequences inserted in the correct reading frame and orientation, can produce fusion proteins. For instance, kgtl 1 will produce fusion proteins whose amino termini consist of B-galactosidase amino acid sequences and whose carboxy termini consist of a foreign polypeptide. Antigenic epitopes of a subject H. pylori polypeptide can then be detected with antibodies, as, for example, reacting nitrocellulose filters lifted from infected plates with anti-H. pylori polypeptide antibodies. Phage, scored by this assay, can then be isolated from the infected plate. Thus, the presence of H pylori gene WO 98/18323 PCTIUS97/19575 -56homologs can be detected and cloned from other species, and alternate isoforms (including splicing variants) can be detected and cloned.

VIII. Kits Containing Nucleic Acids. Polvpeptides or Antibodies of the Invention The nucleic acid, polypeptides and antibodies of the invention can be combined with other reagents and articles to form kits. Kits for diagnostic purposes typically comprise the nucleic acid, polypeptides or antibodies in vials or other suitable vessels.

Kits typically comprise other reagents for performing hybridization reactions, polymerase chain reactions (PCR), or for reconstitution of lyophilized components, such as aqueous media, salts, buffers, and the like. Kits may also comprise reagents for sample processing such as detergents, chaotropic salts and the like. Kits may also comprise immobilization means such as particles, supports, wells, dipsticks and the like.

Kits may also comprise labeling means such as dyes, developing reagents, radioisotopes, fluorescent agents, luminescent or chemiluminescent agents, enzymes, intercalating agents and the like. With the nucleic acid and amino acid sequence information provided herein, individuals skilled in art can readily assemble kits to serve their particular purpose. Kits further can include instructions for use.

IX. Drug Screening Assays Using H. pylori Polypeptides By making available purified and recombinant H. pylori polypeptides, the present invention provides assays which can be used to screen for drugs which are either agonists or antagonists of the normal cellular function, in this case, of the subject H.

pylori polypeptides, or of their role in intracellular signaling. Such inhibitors or potentiators may be useful as new therapeutic agents to combat H. pylori infections in humans. A variety of assay formats will suffice and, in light of the present inventions, will be comprehended by the skilled artisan.

In many drug screening programs which test libraries of compounds and natural extracts, high throughput assays are desirable in order to maximize the number of compounds surveyed in a given period of time. Assays which are performed in cell-free systems, such as may be derived with purified or semi-purified proteins, are often preferred as "primary" screens in that they can be generated to permit rapid development and relatively easy detection of an alteration in a molecular target which is mediated by a test compound. Moreover, the effects of cellular toxicity and/or bioavailability of the test compound can be generally ignored in the in vitro system, the assay instead being focused primarily on the effect of the drug on the molecular target as may be manifest in an alteration of binding affinity with other proteins or change in enzymatic properties of the molecular target. Accordingly, in an exemplary screening assay of the present WO 98/18323 PCT/US97/19575 -57invention, the compound of interest is contacted with an isolated and purified H. pylori polypeptide.

Screening assays can be constructed in vitro with a purified H. pylori polypeptide or fragment thereof, such as an H. pylori polypeptide having enzymatic activity, such that the activity of the polypeptide produces a detectable reaction product.

The efficacy of the compound can be assessed by generating dose response curves from data obtained using various concentrations of the test compound. Moreover, a control assay can also be performed to provide a baseline for comparison. Suitable products include those with distinctive absorption, fluorescence, or chemi-luminescence properties, for example, because detection may be easily automated. A variety of synthetic or naturally occurring compounds can be tested in the assay to identify those which inhibit or potentiate the activity of the H. pylori polypeptide. Some of these active compounds may directly, or with chemical alterations to promote membrane permeability or solubility, also inhibit or potentiate the same activity enzymatic activity) in whole, live H. pylori cells.

This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references and published patent applications cited throughout this application are hereby incorporated by reference.

EXEMPLIFICATION

I. Cloning and Sequencing of H. pylori DNA H. pylori chromosomal DNA was isolated according to a basic DNA protocol outlined in Schleif R.F. and Wensink Practical Methods in Molecular Biology, p.98, Springer-Verlag, NY., 1981, with minor modifications. Briefly, cells were pelleted, resuspended in TE (10 mM Tris, 1 mM EDTA, pH 7.6) and GES lysis buffer (5.1 M guanidium thiocyanate, 0.1 M EDTA, pH 8.0, 0.5% N-laurylsarcosine) was added. Suspension was chilled and ammonium acetate (NH 4 Ac) was added to final concentration of 2.0 M. DNA was extracted, first with chloroform, then with phenolchloroform, and reextracted with chloroform. DNA was precipitated with isopropanol, washed twice with 70% EtOH, dried and resuspended in TE.

Following isolation whole genomic H. pylori DNA was nebulized (Bodenteich et al., Automated DNA Sequencing and Analysis Venter, Academic Press, 1994) to a median size of 2000 bp. After nebulization, the DNA was concentrated and separated on a standard 1% agarose gel. Several fractions, corresponding to WO 98/18323 PCTIUS97/19575 -58approximate sizes 900-1300 bp. 1300-1700 bp, 1700-2200 bp, 2200-2700 bp, were excised from the gel and purified by the GeneClean procedure (Bio 101, Inc.).

The purified DNA fragments were then blunt-ended using T4 DNA polymerase.

The healed DNA was then ligated to unique BstXI-linker adapters in 100-1000 fold molar excess. These linkers are complimentary to the BstXI-cut pMPX vectors, while the overhang is not self-complimentary. Therefore, the linkers will not concatemerize nor will the cut-vector religate itself easily. The linker-adopted inserts were separated from the unincorporated linkers on a 1% agarose gel and purified using GeneClean. The linker-adopted inserts were then ligated to each of the 20 pMPX vectors to construct a series of "shotgun" subclone libraries. The vectors contain an out-of-frame lacZ gene at the cloning site which becomes in-frame in the event that an adapter-dimer is cloned, allowing these to be avoided by their blue-color.

All subsequent steps were based on the multiplex DNA sequencing protocols outlined in Church G.M. and Kieffer-Higgins Science 240:185-188, 1988. Only major modifications to the protocols are highlighted. Briefly, each of the 20 vectors was then transformed into DH5a competent cells (Gibco/BRL, DH5a transformation protocol). The libraries were assessed by plating onto antibiotic plates containing ampicillin, methicillin and IPTG/Xgal. The plates were incubated overnight at 370C.

Successful transformants were then used for plating of clones and pooling into the multiplex pools. The clones were picked and pooled into 40 ml growth medium cultures. The cultures were grown overnight at 370C. DNA was purified using the Qiagen Midi-prep kits and Tip-100 columns (Qiagen, Inc.). In this manner, 100 gg of DNA was obtained per pool. Fifteen 96-well plates of DNA were generated to obtain a 5-10 fold sequence redundancy assuming 250-300 base average read-lengths.

These purified DNA samples were then sequenced using the multiplex DNA sequencing based on chemical degradation methods (Church G.M. and Kieffer-Higgins Science 240:185-188, 1988) or by Sequithrem (Epicenter Technologies) dideoxy sequencing protocols. The sequencing reactions were electrophoresed and transferred onto nylon membranes by direct transfer electrophoresis from 40 cm gels (Richterich P.

and Church Methods in Enzymology 218:187-222, 1993) or by electroblotting (Church, supra). 24 samples were run per gel. 45 successful membranes were produced by chemical sequencing and 8 were produced by dideoxy sequencing. The DNA was covalently bound to the membranes by exposure to ultraviolet light, and hybridized with labeled oligonucleotides complimentary to tag sequences on the vectors (Church, supra).

The membranes were washed to rinse off non-specifically bound probe, and exposed to X-ray film to visualize individual sequence ladders. After autoradiography, the hybridized probe was removed by incubation at 650 C, and the hybridization cycle

A

WO 98/18323 PCT/US97/19575 -59repeated with another tag sequence until the membrane had been probed 38 times for chemical sequencing membranes and 10 times for the dideoxy sequencing membranes.

Thus, each gel produced a large number of films, each containing new sequencing information. Whenever a new blot was processed, it was initially probed for an internal standard sequence added to each of the pools.

Digital images of the films were generated using a laser-scanning densitometer (Molecular Dynamics, Sunnyvale, CA). The digitized images were processed on computer workstations (VaxStation 4000's) using the program REPLICATM (Church et al., Automated DNA Sequencing and Analysis Venter, Academic Press, 1994).

Image processing included lane straightening, contrast adjustment to smooth out intensity differences, and resolution enhancement by iterative gaussian deconvolution.

The sequences were then automatically picked in REPLICATM and displayed for interactive proofreading before being stored in a project database. The proofreading was accomplished by a quick visual scan of the film image followed by mouse clicks on the bands of the displayed image to modify the base calls. Many of the sequence errors could be detected and corrected because multiple sequence reads covering the same portion of the genomic DNA provide adequate sequence redundancy for editing. Each sequence automatically received an identification number (corresponding to microtiter plate, probe information, and lane set number). This number serves as a permanent identifier of the sequence so it is always possible to identify the original of any particular sequence without recourse to a specialized database.

Routine assembly of H. pylori sequences was done using the program FALCON (Church, Church et al., Automated DNA Sequenicng and Analysis Venter, ed.), Academic Press, 1994). This program has proven to be fast and reliable for most sequences. The assembled contigs were displayed using a modified version of GelAssemble, developed by the Genetics Computer Group (GCG) (Devereux et al., Nucleic Acid Res. 12:387-95, 1984) that interacts with REPLICA T M This provided for an integrated editor that allows multiple sequence gel images to be instantaneously called up from the REPLICA T M database and displayed to allow rapid scanning of contigs and proofreading of gel traces where discrepancies occurred between different sequence reads in the assembly.

II. Identification, cloning and expression of recombinant H. pylori DNA sequences To facilitate the cloning, expression and purification of membrane and secreted proteins from H. pylori a powerful gene expression system, the pET System (Novagen), for cloning and expression of recombinant proteins in E. coli, was selected. Also, a DNA sequence encoding a peptide tag, the His-Tag, was fused to the 3' end of DNA WO 98/18323 PCT/US97/19575 sequences of interest in order to facilitate purification of the recombinant protein products. The 3' end was selected for fusion in order to avoid alteration of any terminal signal sequence. The exception to the above was ppiB, a gene cloned for use as a control in the expression studies. In this study, the sequence for H. pylori ppiB contains a DNA sequence encoding a His-Tag fused to the 5' end of the full length gene, because the protein product of this gene does not contain a signal sequence and is expressed as a cytosolic protein.

PCR Amplification and cloning of DNA sequences containing ORF's for membrane and secreted proteins from the J99 Strain of Helicobacter pylori.

Sequences chosen (from the list of the DNA sequences of the invention) for cloning from the J99 strain of H. pylori were prepared for amplification cloning by polymerase chain reaction (PCR). Synthetic oligonucleotide primers (Table 3) specific for the 5' and 3' ends of open reading frames (ORFs) were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5' end of the sequence) were designed to include an NcoI cloning site at the extreme 5' terminus, except for HpSeq. 4821082 where Ndel was used. These primers were designed to permit initiation of protein translation at a methionine residue followed by a valine residue and the coding sequence for the remainder of the native H. pylori DNA sequence. An exception is H. pylori sequence 4821082 where the initiator methionine is immediately followed by the remainder of the native H. pylori DNA sequence. All reverse primers (specific for the 3' end of any H. pylori ORF) included a EcoRI site at the extreme 5' terminus to permit cloning of each H. pylori sequence into the reading frame of the pET-28b. The pET-28b vector provides sequence encoding an additional 20 carboxy-terminal amino acids (only 19 amino acids in HpSeq. 26380318 and HpSeq. 14640637) including six histidine residues (at the extreme C-terminus), which comprise the His-Tag. An exception to the above, as noted earlier, is the vector construction for the ppiB gene. A synthetic oligonucleotide primer specific for the end of ppiB gene encoded a BamHI site at its extreme 5' terminus and the primer for the 3' end of the ppiB gene encoded a Xhol site at its extreme 5' terminus.

WO 98/18323 WO 8/1323PCT[US9 7/19575 61 TABLE 3 Oligonucieotide primers used for PCR amplification of H. pylori DNA seqiuences Outer membrane Forward primer 5' to 3' Reverse Primer 5' to 3' Proteins Protein 16225006 5'-TATACCATGGTGGG CGCTAA-3' (SEQ ID ATGAATTCGAGTAAG NO:147) GATT-.TTG-3' (SEQ ID 148) Protein 26054702 51- TTAACCATGGTGAAA TAGAATTCGCATAAC AGCGATA-3' (SEQ ID GATCAATC-3- (SEQ ID 149) NO: 150) Protein 7116626 ATATCCATGGTGAGT ATGAATTCAATTTTT TTGATGA-3- (SEQ ID TATTTTGCCA-3' (SEQ 15 1) ID NO: 152) Protein 29479681 AATTCCATGGTGGGG ATGAATTCTCGATAG GCTATG-3' (SEQ ID CCAAAATC-3' (SEQ ID NO:153) NO: 154) Protein 14640637 AATTCCATGGTGCAT AAGAATTCTCTAGCA AACTTCCATT-3' (SEQ TCCAAATGGA-3' (SEQ NO: 155) ID NO: 156) Periplasmic/ Secreted Pro teins Protein 30100332 5'-ATTTCCATGGTCATG TCTCATATT-3'(SEQ ID ATGAATTCCATCTTT NO:157) TATTCCAC-3' (SEQ ID 158) Protein 4721061 5'-AACCATGGTGATTT TAAGCATTGAAAG-3' AAGAATTCCACTCA (SEQ ID NO: 159) AAATTTTTTAACAG-3' ID NO: 160) Other Surface Proteins Protein 4821082 5'-GATCATCCATATGTT ATCTTCTAAT-3' (SEQ TGAATTCAACCATTT ID NOA161) TAACCCTG-3' (SEQ ID NO: 162) WO 98/18323 PCT/US97/19575 -62- Protein 978477 5'-TATACCATGGTGAA ATTTTTTCTTTTA-3' AGAATTCAATTGCG (SEQ ID NO: 163) TCTTGTAAAAG-3' (SEQ ID NO:164) Inner Membrane Protein Protein 26380318 5'-TATACCATGGTGAT GGACAAACTC-3' (SEQ GGGGCGATA-3' (SEQ ID NO: 165) ID NO: 166) Cytoplasmic Protein ppi 5'-TTATGGATCCAAAC CAATTAAAACT-3' (SEQ GAGAAGGGC-3' (SEQ ID NO: 167) ID NO: 168) Genomic DNA prepared from the J99 strain ofH. pylori (ATCC #55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) was used as the source of template DNA for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). To amplify a DNA sequence containing an H. pylori ORF, genomic DNA nanograms) was introduced into a reaction vial containing 2 mM MgCl 2 1 micromolar synthetic oligonucleotide primers (forward and reverse primers) complementary to and flanking a defined H. pylori ORF, 0.2 mM of each deoxynucleotide triphosphate: dATP, dGTP. dCTP, dTTP and 2.5 units of heat stable DNA polymerase (Amplitaq, Roche Molecular Systems. Inc., Branchburg, NJ, USA) in a final volume of 100 microliters. The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus/ GeneAmp PCR System 9600 thermal cycler: Protein 26054702, Protein 7116626, Protein 29479681, Protein 30100332, and Protein 4821082; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 16225006; Denaturation at 94 0 C for 2 min.

WO 98/18323 PCT/US97/19575 -63cycles at 95 0 C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reaction was concluded at 72 0 C for 6 minutes.

Protein 4721061; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 36 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 60 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 26380318; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 38 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 62 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 14640637; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 33 0 C for 15 sec and 72 0 C for 1.5 min cycles at 94 0 C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Conditions for amplification of H. pylori ppiB; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 32 0 C for 15 sec and 72 0 C for 1.5 min cycles at 94 0 C for 15 sec, 56 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes Upon completion of thermal cycling reactions, each sample of amplified DNA was washed and purified using the Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA). All amplified DNA samples were subjected to digestion with the restriction endonucleases, NcoI and EcoRI (New England BioLabs, Beverly, MA, USA), or in the case of HpSeq. 4821082 (SEQ ID NO: 1309), with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). DNA samples were then subjected to electrophoresis on 1.0 NuSeive (FMC BioProducts, Rockland, ME USA) agarose gels. DNA was visualized by exposure to ethidium bromide and long wave uv irradiation. DNA contained in slices WO 98/18323 PCT/US97/19575 -64isolated from the agarose gel was purified using the Bio 101 GeneClean Kit protocol (Bio 101 Vista, CA, USA).

Cloning of H. pylori DNA sequences into the pET-28b prokaryotic expression vector.

The pET-28b vector was prepared for cloning by digestion with NcoI and EcoRI, or in the case of H. pylori protein 4821082 with Ndel and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). In the case of cloning ppiB, the pET-28a vector, which encodes a His-Tag that can be fused to the end of an inserted gene, was used and the cloning site prepared for cloning with the ppiB gene by digestion with BamHI and Xhol restriction endonucleases.

Following digestion, DNA inserts were cloned (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994) into the previously digested pET-28b expression vector, except for the amplified insert for ppiB, which was cloned into the pET-28a expression vector. Products of the ligation reaction were then used to transform the BL21 strain of E coli (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994) as described below.

Transformation of competent bacteria with recombinant plasmids Competent bacteria, E coli strain BL21 or E. coli strain BL21(DE3), were transformed with recombinant pET expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Briefly, 1 microliter ofligation reaction was mixed with 50 microliters of electrocompetent cells and subjected to a high voltage pulse, after which, samples were incubated in 0.45 milliliters SOC medium yeast extract, 2.0 tryptone, 10 mM NaCI, 2.5 mM KCI, 10 mM MgC12, 10 mM MgSO4 and mM glucose) at 37 0 C with shaking for 1 hour. Samples were then spread on LB agar plates containing 25 microgram/ml kanamycin sulfate for growth overnight.

Transformed colonies of BL21 were then picked and analyzed to evaluate cloned inserts as described below.

Identification of recombinant pET expression plasmids carrying H. pylori sequences Individual BL21 clones transformed with recombinant pET-28b-H.pylori ORFs were analyzed by PCR amplification of the cloned inserts using the same forward and reverse primers, specific for each H. pylori sequence, that were used in the original PCR amplification cloning reactions. Successful amplification verified the integration of the H. pylori sequences in the expression vector (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994).

WO 98/18323 PCT/US97/19575 Isolation and Preparation ofplasmid DNA from BL21 transformants Individual clones of recombinant pET-28b vectors carrying properly cloned H.

pylori ORFs were picked and incubated in 5 mis of LB broth plus 25 microgram/ml kanamycin sulfate overnight. The following day plasmid DNA was isolated and purified using the Qiagen plasmid purification protocol (Qiagen Inc., Chatsworth, CA,

USA).

Expression of recombinant H. pylori sequences in E. coli The pET vector can be propagated in any E. coli K-12 strain e.g. HMS174, HB101, JM109, DH5, etc. for the purpose of cloning or plasmid preparation. Hosts for expression include E. coli strains containing a chromosomal copy of the gene for T7 RNA polymerase. These hosts are lysogens of bacteriophage DE3, a lambda derivative that carries the lacI gene, the lacUV5 promoter and the gene for T7 RNA polymerase.

T7 RNA polymerase is induced by addition of isopropyl-B-D-thiogalactoside

(IPTG),

and the T7 RNA polymerase transcribes any target plasmid, such as pET-28b, carrying a T7 promoter and a gene of interest. Strains used include: BL21(DE3) (Studier, F.W., Rosenberg, Dunn, and Dubendorff, J.W. (1990) Meth. Enzymol. 185, 60-89).

To express recombinant H. pylori sequences, 50 nanograms of plasmid DNA isolated as described above was used to transform competent BL21 (DE3) bacteria as described above (provided by Novagen as part of the pET expression system kit). The lacZ gene (beta-galactosidase) was expressed in the pET-System as described for the H.

pylori recombinant constructions. Transformed cells were cultured in SOC medium for 1 hour, and the culture was then plated on LB plates containing 25 micrograms/ml kanamycin sulfate. The following day, bacterial colonies were pooled and grown in LB medium containing kanamycin sulfate (25 micrograms/ml) to an optical density at 600 nM of 0.5 to 1.0 O.D. units, at which point, 1 millimolar IPTG was added to the culture for 3 hours to induce gene expression of the H. pylori recombinant DNA constructions.

After induction of gene expression with IPTG, bacteria were pelleted by centrifugation in a Sorvall RC-3B centrifuge at 3500 x g for 15 minutes at 4 0 C. Pellets were resuspended in 50 milliliters of cold 10 mM Tris-HCl, pH 8.0, 0.1 M NaCI and 0.1 mM EDTA (STE buffer). Cells were then centrifuged at 2000 x g for 20 min at 4 0

C.

Wet pellets were weighed and frozen at -80 0 C until ready for protein purification.

III. Purification of recombinant proteins from E. coli Analytical Methods The concentrations of purified protein preparations were quantified spectrophotometrically using absorbance coefficients calculated from amino acid WO 98/18323 PCT/US97/19575 -66content (Perkins, S.J. 1986 Eur. J. Biochem. 157, 169-180). Protein concentrations were also measured by the method of Bradford, M.M. (1976) Anal. Biochem. 72, 248-254, and Lowry, Rosebrough, Farr, A.L. Randall, R.J. (1951) J. Biol. Chem. 193, pages 265-275, using bovine serum albumin as a standard.

SDS-polyacrylamide gels (12% or 4.0 to 25 acrylamide gradient gels) were purchased from BioRad (Hercules, CA, USA), and stained with Coomassie blue.

Molecular weight markers included rabbit skeletal muscle myosin (200 kDa), E. coli galactosidase (116 kDa), rabbit muscle phosphorylase B (97.4 kDa), bovine serum albumin (66.2 kDa), ovalbumin (45 kDa), bovine carbonic anhydrase (31 kDa), soybean trypsin inhibitor (21.5 kDa), egg white lysozyme (14.4 kDa) and bovine aprotinin kDa).

1. Purification of soluble proteins All steps were carried out at 4 0 C. Frozen cells were thawed, resuspended in volumes of lysis buffer (20 mM Tris, pH 7.9, 0.5 M NaCI, 5 mM imidazole with glycerol, 0.1 2-mercaptoethanol, 200 4g/ ml lysozyme, 1 mM phenylmethylsulfonyl fluoride (PMSF), and 10 ug/ml each of leupeptin, aprotinin, pepstatin, L-1-chloro-3-[4tosylamido]-7-amino-2-heptanone (TLCK), L-1-chloro-3-[4-tosylamido]-4-phenyl-2butanone (TPCK), and soybean trypsin inhibitor, and ruptured by several passages through a small volume microfluidizer (Model M- 10S, Microfluidics International Corporation, Newton, MA). The resultant homogenate was made 0.1 Brij 35, and centrifuged at 100,000 x g for 1 hour to yield a clear supernatant (crude extract).

Following filtration through a 0.8 pm Supor filter (Gelman Sciences, FRG) the crude extract was loaded directly onto a Ni 2 nitrilotriacetate-agarose (NTA) with a milliliter bed volume (Hochuli, Dbeli, and Schacheer, A. (1987) J.

Chromatography 411, 177-184) pre-equilibrated in lysis buffer containing 10 glycerol, 0.1 Brij 35 and 1 mM PMSF. The column was washed with 250 ml (50 bed volumes) of lysis buffer containing 10 glycerol, 0.1 Brij 35, and was eluted with sequential steps of lysis buffer containing 10 glycerol, 0.05 Brij 35, 1 mM PMSF, and 20, 100, 200, and 500 mM imidazole in succession. Fractions were monitored by absorbance at OD 2 8 0 nm, and peak fractions were analyzed by SDS-PAGE. Fractions containing the recombinant protein eluted at 100 mM imidazole.

Recombinant protein 14640637 and proteins, beta-galactosidase (lacZ) andpeptidylprolyl cis-trans isomerase (ppiB) Fractions containing the recombinant proteins from the Ni2+-NTA-agarose columns were pooled and then concentrated to approximately 5 ml by centrifugal WO 98/18323 PCT/US97/19575 -67 filtration (Centriprep-10, Amicon, MA), and loaded directly onto a 180-ml column (1.6 X 91 cm) of Sephacryl S-100 HR gel filtration medium equilibrated in Buffer A (10 mM Hepes, pH 7.5, 150 mM NaCI, 0.1 mM EGTA) and run in Buffer A at 18 ml/h.

Fractions containing the recombinant protein were identified by absorbance at 280 nm and analyzed by SDS-PAGE. Fractions were pooled and concentrated by centrifugal filtration.

Recombinant protein 7116626 Fractions containing the recombinant protein from the Ni 2 -NTA-agarose column were pooled and dialyzed overnight against 1 liter of dialysis buffer (10 mM MOPS, pH 6.5, 50 mM NaCI, 0.1 mM EGTA, 0.02% Brij 35 and 1 mM PMSF). In the morning, a fine white precipitate was removed by centrifugation and the resulting supernatant was loaded onto an 8 ml (8 x 75 mm) MonoS high performance liquid chromatography column (Pharmacia Biotechnology, Inc.. Piscataway, NJ, USA) equilibrated in buffer B (10 mM MOPS, pH 6.5, 0.1 mM EGTA) containing 50 mM NaCI. The column was washed with 10 bed volumes of buffer B containing 50 mM NaC1, and developed with a 50-ml linear gradient of increasing NaCI (50 to 500 mM).

Recombinant protein 7116626 eluted as a sharp peak at 300 mM NaCI.

2. Purification of insoluble proteins from inclusion bodies The following steps were carried out at 4 0 C. Cell pellets were resuspended in lysis buffer with 10% glycerol 200 p.g/ ml lysozyme, 5 mM EDTA, ImM PMSF and 0.1 -mercaptoethanol. After passage through the cell disrupter, the resulting homogenate was made 0.2 deoxycholate, stirred 10 minutes, then centrifuged at 20,000 x g, for min. The pellets were washed with lysis buffer containing 10 glycerol, 10 mM EDTA, 1% Triton X-100, 1 mM PMSF and 0.1% -mercaptoethanol, followed by several washes with lysis buffer containing 1 M urea, 1 mM PMSF and 0.1 2mercaptoethanol. The resulting white pellet was composed primarily of inclusion bodies, free of unbroken cells and membranous materials..

Recombinant proteins 26054702, 16225006, 30100332, 4721061 The following steps were carried out at room temperature. Purified inclusion bodies were dissolved in 20 ml 8.0 M urea in lysis buffer with 1 mM PMSF and 0.1 2-mercaptoethanol, and incubated at room temperature for 1 hour. Materials that did not dissolve were removed by centrifugation. The clear supematant was filtered, then loaded onto a Ni 2 -NTA agarose column pre-equilibrated in 8.0 M urea in Lysis Buffer. The column was washed with 250 ml (50 bed volumes) of lysis buffer WO 98/18323 PCT/US97/19575 -68containing 8 M urea, 1.0 mM PMSF and 0.1 2-mercaptoethanol, and developed with sequential steps of lysis buffer containing 8M urea, 1 mM PMSF, 0.1 2mercaptoethanol and 20, 100, 200, and 500 mM imidazole in succession. Fractions were monitored by absorbance at OD 2 80 nm, and peak fractions were analyzed by SDS- PAGE. Fractions containing the recombinant protein eluted at 100 mM imidazole.

Recombinant proteins 29479681, 26380318 The pellet containing the inclusion bodies was solubilized in buffer B containing 8 M urea, 1 mM PMSF and 0.1 2-mercaptoethanol, and incubated for 1 hour at room temperature. Insoluble materials were removed by centrifugation at 20,000 x g for min, and the cleared supernatant was loaded onto a 15 ml (1.6 x 7.5 cm) SP-Sepharose column pre-equilibrated in buffer B, 6 M urea, 1 mM PMSF, 0.1 2-mercaptoethanol.

After washing the column with 10 bed volumes, the column was developed with a linear gradient from 0 to 500 mM NaCl.

Dialysis and concentration of protein samples Urea was removed slowly from the protein samples by dialysis against Trisbuffered saline (TBS; 10 mM Tris pH 8.0, 150 mM NaCI) containing 0.5 deoxycholate (DOC) with sequential reduction in urea concentration as follows; 6M, 4M, 3M, 2M, 1M, 0.5 M and finally TBS without any urea. Each dialysis step was conducted for a minimum of 4 hours at room temperature.

After dialysis, samples were concentrated by pressure filtration using Amicon stirred-cells. Protein concentrations were measured using the methods of Perkins (1986 Eur. J. Biochem. 157, 169-180), Bradford ((1976) Anal. Biochem. 72, 248-254) and Lowry ((1951) J. Biol. Chem. 193, pages 265-275).

The recombinant proteins purified by the methods described above are summarized in Table 4 below.

TABLE 4 J99 Homolog Gene Bacterial cell Method of Relative Final Composit Sequence identified symbol fraction used to purification MW on concentratio ionof Identifier by Blast of purify SDS- n of purified buffer Homolog recombinant PAGE gel protein proteins Outer Membrane Proteins 16225006 P28635 YEAC Inclusion bodies His-Tag 18 kDa 5 mg/ml B 26054702 P15929 flgH Inclusion bodies His-Tag 37 kDa 1.18 mg/mi B WO 98/18323 WO 9818323PCT/US97/19575 69 as dry 7116626 P26093 e(P4) Soluble fraction H is-Tag 29 kDa 0.8 mg/mi A mg/mi C 29479681 P 13036 fecA Inclusions SP- 23 kDa 2.36 mg/mI B Sepharose mi B as dry 14640637 P16665 TPFI Soluble fraction His-Tag 17 kDa 2.4 mg/m I A gel filtration S 100 HRjJ Periplasmic/Secreted Protein 3010032 P23847 dppA Inclusion bodies His-Tag I I kDa 2.88 mg/mI B 4721061 P36 175 GCP Inclusion bodies His-Tag 38 kDa 2.8 mg/m I B Other Surface Proteins 4821082 P08089 M Inclusion bodies His-Tag 20 kDa 1. 16 mg/m I B protein 978477 L28919 FBP54 Inclusion bodies SP- 44 kDa 2.56 mg/mi B Sepharose Inner Memb Irane Proteins10. gm B 26380318 1P15933 ING {Inclusion bodies SP- 11 kDa 22 mg/mi B Sepharose Control Proteins with His-Tag P00722 lacZ Soluble fraction His-Tag 11 llkDa 10 mg/mi A gel filtration S200 HR Soluble fraction His-Tag 121lkDa 14.4 mg/mi A filtration S 100 HR Buffer composition mM Hepes pH 7.5, 150 mM NaCI, 0. 1 mM EGTA B= 10 mM Tris pH 8.0. 150 mM NaC. 0.5 DOGC___ C= 10 mM MOPS pH 6.5, 300 mM NaC, 0.1 EGTA WO 98/18323 PCT/US97/19575 IV. Analysis of H. pylori proteins as Vaccine candidates To investigate the immunomodulatory effect of H. pylori proteins, a mouse/H.

pylori model was used. This model mimics the human H. pylori infection in many respects. The focus is on the effect of oral immunization in H pylori infected animals in order to test the concept of therapeutic oral immunotherapy.

Animals Female SPF BALB/c mice were purchased from Bomholt Breeding center (Denmark). They were kept in ordinary makrolon cages with free supply of water and food. The animals were 4-6 weeks old at arrival.

Infection After a minimum of one week of acclimatization, the animals were infected with a type 2 strain (VacA negative) of H. pylori (strain 244. originally isolated from an ulcer patient). In our hands, this strain has earlier proven to be a good colonizer of the mouse stomach. The bacteria were grown overnight in Brucella broth supplemented with 10 fetal calf serum, at 37 0 C in a microaerophilic atmosphere (10% CO2, 5%02). The animals were given an oral dose of omeprazole (400 pmol/kg) and 3-5 h after this an oral inoculation of H. pylori in broth (approximately 108 cfu/animal). Positive take of the infection was checked in some animals 2-3 weeks after the inoculation.

Antigens Recombinant H. pylori antigens were chosen based on their association with externally exposed H. pylori cell membrane. These antigens were selected from the following groups: Outer Membrane Proteins; Periplastic/Secreted proteins; Outer Surface proteins; and Inner Membrane proteins. All recombinant proteins were constructed with a hexa-HIS tag for purification reasons and the non-Helicobacter pylori control protein (b-galactosidase from E. coli; LacZ), was constructed in the same way.

All antigens were given in a soluble form, i.e. dissolved in either a HEPES buffer or in a buffer containing 0.5% Deoxycholate (DOC).

The antigens are listed in Table 5 below.

Table Helicobacter pylori proteins Outer membrane Proteins Protein 7116626 Protein 4721061 WO 98/18323 PCT/US97/19575 -71 Protein 16225006 Protein 29479681 Protein 14640637 Periplasmic/Secreted Proteins Protein 30100332 Other cell envelope proteins Protein 4821082 Flagella-associated proteins Protein 26380318 Control proteins b-galactosidase (LacZ) Immunizations Ten animals in each group were immunized 4 times over a 34 day period (day 1, 25 and 35). Purified antigens in solution or suspension were given at a dose of 100 mg/mouse. As an adjuvant, the animals were also given 10 pg/mouse of Cholera toxin (CT) with each immunization. Omeprazole (400 mmol/kg) was given orally to the animals 3-5 h prior to immunization as a way of protecting the antigens from acid degradation. Infected control animals received HEPES buffer CT or DOC buffer CT. Animals were sacrificed 2-4 weeks after final immunization. A general outline of the study is shown in Table 6 below.

Table 6 Study outline, therapeutic immunization: Mice were all infected with H. pylori strain Ah244 at day Substance Mouse strain Dose/mouse Dates for dosing 1. Controls, PBS Balb/c 0.3 ml 0, 14, 24, 34 2. Cholera toxin, 10 pg Balb/c 0.3 ml 0, 14,24,34 3. Protein 16225006, 100 tg CT 10 jg Balb/c 0.3 ml 0, 14, 24, 34 4. Protein 26054702, 100 pg CT 10 pg Balb/c 0.3 ml 0, 14, 24, 34 WO 98/18323 PCT/US97/19575 -72- Protein 26380318, 100 gg CT 10 pg Balb/c 0.3 ml 0, 14,24,34 6. Protein 29479681, 100 p.g CT 10 g Balb/c 0.3 ml 0, 14, 24, 34 7. Protein 30100332, 100 Lg CT 10 gg Balb/c 0.3 ml 0, 14, 24, 34 8. Protein 4721061, 100 g CT 10 pg Balb/c 0.3 ml 0, 14,24,34 9. Protein 4821082, 100 pg CT 10 pg Balb/c 0.3 ml 0, 14, 24, 34 Protein 7116626, 100 ug CT 10 Lg Balb/c 0.3 ml 0, 14, 24, 34 11.Protein 14640637, 100 ig CT 10 jig Balb/c 0.3 ml 0, 14, 24, 34 Analysis of infection Mucosal infection: The mice were sacrificed by CO 2 and cervical dislocation.

The abdomen was opened and the stomach removed. After cutting the stomach along the greater curvature, it was rinsed in saline. The mucosa from the antrum and corpus of an area of 25mm 2 was scraped separately with a surgical scalpel. The mucosa scraping was suspended in Brucella broth and plated onto Blood Skirrow selective plates. The plates were incubated under microaerophilic conditions for 3-5 days and the number of colonies was counted. The identity of H. pylori was ascertained by urease and catalase test and by direct microscopy or Gram staining.

The urease test was performed essentially as follows. The reagent, Urea Agar Base Concentrate. was purchased from DIFCO Laboratories, Detroit, MI (Catalog 0284-61-3). Urea agar base concentrate was diluted 1:10 with water. 1 ml of if the diluted concentrate was mixed with 100-200 ml of actively growing H pylori cells.

Color change to magenta indicated that cells were urease positive.

The catalase test was performed essentially as follows. The reagent, Tetramethyl-p-Phenylenediamine, was purchased from Sigma, St. Louis, MO (Catalog T3134). A solution of the regent w/v in water) was prepared. H. pylori cells were swabbed onto Whatman filter paper and overlaid with the 1% solution. Color change to dark blue indicated that the cells were catalase positive.

Serum antibodies: From all mice serum was prepared from blood drawn by heart puncture. Serum antibodies were identified by regular ELISA techniques, where the specific antigens of Helicobacter pylori were plated.

Mucosal antibodies: Gentle scrapings of a defined part of the corpus and of 4 cm of duodenum were performed in 50% of the mice in order to detect the presence of ,1 WO 98/18323 PCT/US97/19575 -73antibodies in the mucous. The antibody titers were determined by regular ELISA technique as for serum antibodies.

Statistical analysis: Wilcoxon-Mann-Whitney sign rank test was used for determination of significant effects of the antigens on Helicobacter pylori colonization.

P<0.05 was considered significant. Because the antrum is the major colonization site for Helicobacter most emphasis was put upon changes in the antral colonization.

Results Antibodies in sera: All antigens tested given together with CT gave rise to a measurable specific titer in serum. The highest responses were seen with Protein 7116626, Protein 4721061, Protein 26380318, Protein 14640637 and Protein 4821082 (see Figure 1).

Antibodies in mucus: In the mucus scrapings, specific antibodies against all antigens tested were seen. By far the strongest response was seen with Protein 30100332, followed by Protein 14640637, and Protein 26380318 (see Figure 2).

Therapeutic immunization effects: All control animals (BALB/c mice) were well colonized with H. pylori (strain AH244) in both antrum and corpus of the stomach. Of the antigens tested 3 proteins (Protein 4721061, Protein 4821082, and Protein 14640637) gave a good and significant reduction and/or eradication of the H. pylori infection. The degree of colonization of the antrum was lower following immunization with Protein 7116626 and Protein 26380318 compared to control. The effect of Proteins 16225006, 29479681, and 30100332 did not differ from control. The control protein lacZ, i.e. the non-H. pylori protein, had no eradication effect and in fact had higher Helicobacter colonization compared to the HEPES CT control. All data are shown in Figures 3 and 4 for proteins dissolved in HEPES and DOC respectively. Data is shown as geometric mean values. n=8-10 Wilcoxon-Mann-Whitney sign rank test p<0.05; x/10 number of mice showing eradication of H. pylori over the total number of mice examined.

The data presented indicate that all of the H. pylori associated proteins included in this study, when used as oral immunogens in conjunction with the oral adjuvant CT, resulted in stimulation of an immune response as measured by specific serum and mucosal antibodies. A majority of the proteins led to a reduction, and in some cases complete clearance of the colonization ofH. pylori in this animal model. It should be noted that the reduction or clearance was due to heterologous protection rather than homologous protection (the polypeptides were based on the H. pylori J99 strain WO 98/18323 PCT/US97/19575 -74sequence and used in the therapeutic immunization studies against a different (AH244) challenge strain, indicating the vaccine potential against a wide variety of H. pylori strains.

The highest colonization in the antrum was seen in animals treated with the non- Helicobacter protein LacZ, indicating that the effects seen with the Helicobacterpylori antigens were specific.

Taken together these data strongly support the use of these H. pylori proteins in a pharmaceutical formulation for the use in humans to treat and/or prevent H. pylori infections.

V. Sequence Variance Analysis of genes in Helicobacter pylori strains Four genes were cloned and sequenced from several strains of H. pylori to compare the DNA and deduced amino acid sequences. This information was used to determine the sequence variation between the H. pylori strain, J99, and other H pylori strains isolated from human patients.

Preparation of Chromosomal DNA.

Cultures of H pylori strains (as listed in Table 9) were grown in BLBB (1% Tryptone, 1% Peptamin 0.1% Glucose, 0.2% Yeast Extract 0.5% Sodium Chloride, Fetal Bovine Serum) to an OD 600 of 0.2. Cells were centrifuged in a Sorvall RC-3B at 3500 x g at 4 0 C for 15 minutes and the pellet resuspended in 0.95 mis of 10 mM Tris- HCI, 0.1 mM EDTA Lysozyme was added to a final concentration of Img/ml along with, SDS to 1% and RNAse A T1 to 0.5mg/ml and 5 units/ml respectively, and incubated at 37 0 C for one hour. Proteinase K was then added to a final concentration of 0.4mg/ml and the sample was incubated at 55 C for more than one hour. NaCl was added to the sample to a concentration of 0.65 M, mixed carefully, and 0.15 ml of CTAB in 0.7M NaCL (final is 1% CTAB/70mM NaCL) was added followed by incubation at 65 0 C for 20 minutes. At this point, the samples were extracted with chloroform:isoamyl alcohol, extracted with phenol, and extracted again with chloroform:isoamyl alcohol. DNA was precipitated with either EtOH (1.5 x volumes) or isopropanol (0.6 x volumes) at -70 0 C for 1Ominutes, washed in 70% EtOH and resuspended in TE.

PCR Amplification and cloning.

Genomic DNA prepared from twelve strains of Helicobacter pylori was used as the source of template DNA for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). To WO 98/18323 PCTIUS97/19575 amplify a DNA sequence containing an H. pylori ORF, genomic DNA (10 nanograms) was introduced into a reaction vial containing 2 mM MgCl 2 1 micromolar synthetic oligonucleotide primers (forward and reverse primers, see Table 7) complementary to and flanking a defined H pylori ORF, 0.2 mM of each deoxynucleotide triphosphate; dATP, dGTP, dCTP, dTTP arind 0.5 units of heat stable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in a final volume of microliters in duplicate reactions.

Table 7 Oliaonucleotide primers used for PCR amplification of H. vilori DNA sequences.

Outer membrane Forward primer 5' to 3' Reverse Primer 5' to 3' Proteins Protein 26054702 (for strains AH4, AHl5, TTAACCATGGTGAAA TAGAATTCGCCTCTA AH61, 5294, 5640, AGCGATA-3' (SEQ ID AAACTTTAG-3' (SEQ AH 18, and AH244) NO:169) ID NO:170) Protein 26054702 (for strains AH5, 5155, TTAACCATGGTGAAA TAGAATTCGCATAAC 7958, AH24,and J99) AGCGATA-3' (SEQ ID GATCAATC-3' (SEQ ID NO:171) NO:172) Protein 7116626 ATATCCATGGTGAGT ATGAATTCAATTTTT TTGATGA-3' (SEQ ID TATTTTGCCA-3'

(SEQ

NO:173) ID NO:174) Protein 29479681 AATTCCATGGCTATC ATGAATTCGCCAAAA CAAATCCG-3' (SEQ ID TCGTAGTATT-3' (SEQ NO:175) ID NO:176) Protein 346 GATACCATGGAATTT TGAATTCGAAAAAGT ATGAAAAAG-3' (SEQ GTAGTTATAC-3' (SEQ ID NO:177) ID NO:178) The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus/ GeneAmp PCR System 9600 thermal cycler: WO 98/18323 PCT/US97/19575 -76- Protein 7116626 and Protein 346; Denaturation at 94C for 2 min, 2 cycles at 94C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 55°C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72C for 6 minutes.

Protein 26054702 for strains AH5, 5155, 7958, AH24,and J99; Denaturation at 94 0 C for 2 min, 2 cycles at 94°C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min cycles at 94 0 C for 15 sec, 55°C for 15 sec and 72 0 C for 1.5 min Reaction was concluded at 72 0 C for 6 minutes.

Protein 26054702 and Protein 294796813 for strains AH4, AH15, AH61, 5294, 5640, AH18, and Hp244; Denaturation at 94 0 C for 2 min, 2 cycles at 94°C for 15 sec, 30 0 C for 20 sec and 72 0 C for 2 min cycles at 94 0 C for 15 sec, 55 0 C for 20 sec and 72 0 C for 2 min Reactions were concluded at 72 0 C for 8 minutes.

Upon completion of thermal cycling reactions, each pair of samples were combined and used directly for cloning into the pCR cloning vector as described below.

Cloning ofH. pylori DNA sequences into the pCR TA cloning vector.

All amplified inserts were cloned into the pCR 2.1 vector by the method described in the Original TA cloning kit (Invitrogen, San Diego, CA). Products of the ligation reaction were then used to transform the TOP OF' (INVaF' in the case of H.

pylori sequence 350) strain of E. coli as described below.

Transformation of competent bacteria with recombinant plasmids Competent bacteria, E coli strain TOPI OF' or E. coli strain INVaF' were transformed with recombinant pCR expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). Briefly, 2 microliters of micromolar BME was added to each vial of 50 microliters of competent cells.

Subsequently, 2 microliters of ligation reaction was mixed with the competent cells and incubated on ice for 30 minutes. The cells and ligation mixture were then subjected to a WO 98/18323 PCT/US97/19575 -77- "heat shock" at 42 0 C for 30 seconds, and were subsequently placed on ice for an additional 2 minutes, after which, samples were incubated in 0.45 milliliters SOC medium yeast extract, 2.0 tryptone, 10 mM NaCI, 2.5 mM KC1, 10 mM MgC12, 10 mM MgSO4 and 20, mM glucose) at 37 0 C with shaking for 1 hour. Samples were then spread on LB agar plates containing 25 microgram/ml kanamycin sulfate or 100 micrograms/ml ampicillan for growth overnight. Transformed colonies of TOP 1 OF' or INVaF' were then picked and analyzed to evaluate cloned inserts as described below.

Identification of recombinant PCR plasmids carrying H. pylori sequences Individual TOPI OF' or INVaF' clones transformed with recombinant pCR- H.pylori ORFs were analyzed by PCR amplification of the cloned inserts using the same forward and reverse primers, specific for each H. pylori sequence, that were used in the original PCR amplification cloning reactions. Successful amplification verified the integration of the H. pylori sequences in the cloning vector (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994).

Individual clones of recombinant pCR vectors carrying properly cloned H. pylori ORFs were picked for sequence analysis. Sequence analysis was performed on ABI Sequencers using standard protocols (Perkin Elmer) using vector-specific primers (as found in PCRII or pCR2.1, Invitrogen, San Diego, CA) and sequencing primers specific to the ORF as listed in Table 8 below.

WO 98/18323 WO 9818323PCTIUS97/19575 78 Table 8 Oligonucleotidg nrimers used for sequencing of HI. 2vlori DNA seqiuences.

Outer membran Fowr primers 5' to 3'Reverse Primers 5' to 3' Proteins n owr Protein 26054702

CCCTTCATTTTAGAAATC

G-3'(SEQ ID NO: 179)

ATTTCAACCAATTCAAT

GCG-3' (SEQ ID NO: 180)

GCCCCTTTTGATTTGAAG

CT-3'(SEQ ID NO: 181)

TCGCTCCAAGATACCAA

GAAGT-3' (SEQ ID NO: 182)

G'FIGAATTAGGGGCAAA

GATCG-3' (SEQ ID NO: 183)

ATGCGTTTTTACCCAAA

GAAGT-3' (SEQ ID NO: 184)

ATAACGCCACTTCCTTAT

TGGT-3' (SEQ ID NO: 185)

CTTTGGGTAAAAACGCA

TC-3' (SEQ I D NO: 186)

CGATCTTTGATCCTAATT

CA-3' (SEQ ID NO: 187) 51-

ATCAAGTTGCCTATGCT

GA-3' (SEQ ID NO: 188) 3~A~ I7,~ (oil rotein 7116626 51- TTGAACACTTTTGATTAT GTC1TI'AGCAAAAATGG GCGG-3' (SEQ ID NO: 189) CGTC-3' (SEQ ID NO: 19 1) 51- 519 GGATTATGCGATTGTTTT

AATGAGCGTAAGAGAGC

ACAAG-3' (SEQ ID CTTC-3' (SEQ ID NO: 192) NO: 190) *otein 479681

CTTATGGGGGTATTGTC

A-3' (SEQ ID NO: 193)

AGCATGTGGGTATCCAG

C-3'(SEQ ID NO: 194)

AGGTTGTTGCCTAAAGA

CT-3' (SEQ ID NO: 195)

CTGCCTCCACCTTTGATC

(SEQ ID NO: 196) WO 98/18323 PCT/US97/19575 -79- Protein 346 ACCAATATCAATTGGCA

CTTGCTTGTCATATCTAG

CT-3' (SEQ ID NO:197) C-3' (SEQ ID NO:199) ACTTGGAAAAGCTCTGC GTTGAAGTGTTGGTGCT (SEQ ID NO:198) A-3' (SEQ ID NO:200) CAAGCAAGTGGTTTGGT

GCCCATAATCAAAAAGC

TTTAG-3' (SEQ ID NO:201) CCAT-3' (SEQ ID NO:203) TGGAAAGAGCAAATCAT

CTAAAACCAAACCACTT

TGAAG-3' (SEQ ID GCT NO:202) TGTC-3' (SEQ ID NO:204) Vector Primers GTAAAACGACGGCCAG-

CAGGAAACAGCTATGAC

3' (SEQ ID NO:205) (SEQ ID NO:206) Results To establish the PCR error rate in these experiments, five individual clones of Protein 26054702, prepared from five separate PCR reaction mixtures from H. pylori strain J99, were sequenced over a total length of 897 nucleotides for a cumulative total of 4485 bases of DNA sequence. DNA sequence for the five clones was compared to a DNA sequence obtained previously by a different method, random shotgun cloning and sequencing. The PCR error rate for the experiments described herein was determined to be 2 base changes out of 4485 bases, which is equivalent to an estimated error rate of less than or equal to 0.04%.

DNA sequence analysis was performed on four different open reading frames identified as genes and amplified by PCR methods from a dozen different strains of the bacterium Helicobacter pylori. The deduced amino acid sequences of three of the four open reading frames that were selected for this study showed statistically significant BLAST homology to defined proteins present in other bacterial species. Those ORFs included: Protein 26054702, homologous to the val A B genes encoding an ABC transporter in F. novicida; Protein 7116626, homologous to lipoprotein e (P4) present in the outer membrane of H. influenzae; Protein 29479681, homologous to fecA, an outer membrane receptor in iron (III) dicitrate transport in E. coli. Protein 346 was identified as an unknown open reading frame, because it showed low homology with sequences in the public databases.

To assess the extent of conservation or variance in the ORFs across various strains of H. pylori, changes in DNA sequence and the deduced'protein sequence were compared to the DNA and deduced protein sequences found in the J99 strain of H.

WO 98/18323 PCT/US97/19575 pylori (see Table 9 below). Results are presented as percent identity to the J99 strain of H. pylori sequenced by random shotgun cloning. To control for any variations in the J99 sequence each of the four open reading frames were cloned and sequenced again from the J99 bacterial strain and that sequence information was compared to the sequence information that had been collected from inserts cloned by random shotgun sequencing of the J99 strain. The data demonstrate that there is variation in the DNA sequence ranging from as little as 0.12 difference (Protein 346, J99 strain) to approximately 7% change (Protein 26054702. strain AH5). The deduced protein sequences show either no variation Protein 346, strains AH18 and AH24) or up to as much as 7.66% amino acid changes (Protein 26054702, Strain Table 9 Multiple Strain DNA Sequence analysis of H. pylori Vaccine Candidates J99 Protein 26054702 2054702 7116626 7116626 29479681 29479681 346 346 Length of Region Sequenced: 248 a.a. 746 nt. 232 a.a. 96 nt. 182 a.a. 548 nt. 273 a.a. 819 nt.

Strain Tested AA Nuc. AA Nuc. AA Nuc. AA Nuc.

identity identity identity identity identity identity identity identity J99 100.00% 100.00% 100.00% 100.00% 100.00% 100.00% 99.63% 99.88% AH244 95.16% 95.04% n.d. n.d. 99.09% 96.71% 98.90% 96.45% AH4 95.97% 95.98% 97.84% 95.83% n.d. n.d. 97.80% 95.73% 92.34% 93.03% 98.28% 96.12% 98.91% 96.90% 98.53% 95.73% 95.16% 94.91% 97.41% 95.98% 99.82% 97.99% 99.63% 96.09% AH61 n.d. n.d. 97.84% 95.98% 99.27% 97.44% n.d. n.d.

5155 n.d. n.d. n.d. n.d. 99.45% 97.08% 98.53% 95.60% 5294 94.35% 94.37% 98.28% 95.40% 99.64% 97.26% 97.07% 95.48% 7958 94.35% 94.10% 97.84% 95.40% n.d. n.d. 99.63% 96.46% 5640 95.16% 94.37% 97.41% 95.69% 99.09% 97.63% 98.53% 95.48% AH 18 n.d. n.d. 98.71% 95.69% 99.64% 97.44% 100.00% 95.97% AH24 94.75% 95.04% 97.84% 95.40% 99.27% 96.71% 100.00% 96.46% not done.

WO 98/18323 PCT/US97/19575 -81 VI. Experimental Knock-Out Protocol for the Determination of Essential H. pylori Genes as Potential Therapeutic Targets Therapeutic targets are chosen from genes whose protein products appear to play key roles in essential cell pathways such as cell envelope synthesis, DNA synthesis, transcription, translation, regulation and colonization/virulence.

The protocol for the deletion of portions of H. pylori genes/ORFs and the insertional mutagenesis of a kanamycin-resistance cassette in order to identify genes which are essential to the cell is modified from previously published methods (Labigne- Roussel et al., 1988, J. Bacteriology 170, pp. 1704-1708; Cover et al.,1994, J. Biological Chemistry 269, pp. 10566-10573; Reyrat et al., 1995, Proc. Natl. Acad. Sci. 92, pp 8768-8772). The result is a gene "knock-out." Identification and Cloning ofH. pylori Gene Sequences The sequences of the genes or ORFs (open reading frames) selected as knock-out targets are identified from the H. pylori genomic sequence and used to design primers to specifically amplify the genes/ORFs. All synthetic oligonucleotide primers are designed with the aid of the OLIGO program (National Biosciences, Inc., Plymouth, MN 55447, USA), and can be purchased from Gibco/BRL Life Technologies (Gaithersburg, MD, USA). If the ORF is smaller than 800 to 1000 base pairs, flanking primers are chosen outside of the open reading frame.

Genomic DNA prepared from the Helicobacter pylori HpJ99 strain (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) is used as the source of template DNA for amplification of the ORFs by PCR (polymerase chain reaction) (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al.. editors, 1994). For the preparation of genomic DNA from H. pylori, see Example I. PCR amplification is carried out by introducing nanograms of genomic HpJ99 DNA into a reaction vial containing 10 mM Tris pH 8.3, mM KC1, 2 mM MgC12, 2 microMolar synthetic oligonucleotide primers (forward=Fl and reverse=Rl), 0.2 mM of each deoxynucleotide triphosphate (dATP,dGTP, dCTP, dTTP), and 1.25 units of heat stable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc.. Branchburg, NJ, USA) in a final volume of microliters. The PCR is carried out with Perkin Elmer Cetus/GeneAmp PCR System 9600 thermal cyclers.

Upon completion of thermal cycling reactions, each sample of amplified DNA is visualized on a 2% TAE agarose gel stained with Ethidium Bromide (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994) to WO 98/18323 PCT/US97/19575 -82determine that a single product of the expected size had resulted from the reaction.

Amplified DNA is then washed and purified using the Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA).

PCR products are cloned into the pT7Blue T-Vector (catalog#69820-1, Novagen, Inc., Madison, WI, USA) using the TA cloning strategy (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). The ligation of the PCR product into the vector is accomplished by mixing a 6 fold molar excess of the PCR product, 10 ng of pT7Blue-T vector (Novagen), 1 microliter of T4 DNA Ligase Buffer (New England Biolabs, Beverly, MA, USA), and 200 units of T4 DNA Ligase (New England Biolabs) into a final reaction volume of 10 microliters. Ligation is allowed to proceed for 16 hours at 16 0

C.

Ligation products are electroporated (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al.. editors, 1994) into electroporationcompetent XL-1 Blue or DH5-a E.coli cells (Clontech Lab., Inc. Palo Alto, CA, USA).

Briefly, 1 microliter of ligation reaction is mixed with 40 microliters of electrocompetent cells and subjected to a high voltage pulse (25 microFarads, 2.5 kV, 200 ohms) after which the samples are incubated in 0.45 ml SOC medium yeast extract, 2% tryptone, 10 mM NaCI, 2.5 mM KCI, 10 mM MgCl2, 10 mM MgSO 4 and mM glucose) at 37 0 C with shaking for 1 hour. Samples are then spread onto LB (10 g/1 bacto tryptone, 5 g/1 bacto yeast extract, 10 g/l sodium chloride) plates containing 100 microgram/ml of Ampicillin, 0.3% X-gal, and 100 microgram/ml IPTG. These plates are incubated overnight at 37 0 C. Ampicillin-resistant colonies with white color are selected, grown in 5 ml of liquid LB containing 100 microgram/ml of Ampicillin, and plasmid DNA is isolated using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

To verify that the correct H.pylori DNA inserts had been cloned, these pT7Blue plasmid DNAs are used as templates for PCR amplification of the cloned inserts, using the same forward and reverse primers used for the initial amplification of the J99 H.pylori sequence. Recognition of the primers and a PCR product of the correct size as visualized on a 2% TAE, ethidium bromide stained agarose gel are confirmation that the correct inserts had been cloned. Two to six such verified clones are obtained for each knock-out target, and frozen at -70 0 C for storage. To minimize errors due to PCR, plasmid DNA from these verified clones are pooled, and used in subsequent cloning steps.

The sequences of the genes/ORFs are again used to design a second pair of primers which flank the region of H. pylori DNA to be either interrupted or deleted (up to 250 basepairs) within the ORFs but are oriented away from each other. The pool of WO 98/18323 PCT/US97/19575 83 circular plasmid DNAs of the previously isolated clones are used as templates for this round of PCR. Since the orientation of amplification of this pair of deletion primers is away from each other, the portion of the ORF between the primers is not included in the resultant PCR product. The PCR product is a linear piece of DNA with H. pylori DNA at each end and the pT7Blue vector backbone between them which, in essence, resultes in the deletion of a portion of the ORFs. The PCR product is visualized on a 1% TAE, ethidium bromide stained agarose gel to confirm that only a single product of the correct size has been amplified.

A Kanamycin-resistance cassette (Labigne-Roussel et al., 1988 J. Bacteriology 170, 1704-1708) is ligated to this PCR product by the TA cloning method used previously (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., editors, 1994). The Kanamycin cassette containing a Campylobacter kanamycin resistance gene is obtained by carrying out an EcoRI digestion of the recombinant plasmid pCTB8:kan (Cover et al.,1994, J. Biological Chemistry 269, pp.

10566-10573). The proper fragment (1.4 kb) is isolated on a 1% TAE gel, and isolated using the QIAquick gel extraction kit (Qiagen, Gaithersburg, MD, USA). The fragment is end repaired using the Klenow fill-in protocol, which involved mixing 4ug of the DNA fragment, 1 microliter of dATP,dGTP, dCTP, dTTP at 0.5 mM, 2 microliter of Klenow Buffer (New England Biolabs) and 5 units of Klenow DNA Polymerase I Large (Klenow) Fragment (New England Biolabs) into a 20 microliter reaction, incubating at 0 C for 15 min, and inactivating the enzyme by heating to 75 0 C for 10 minutes. This blunt-ended Kanamycin cassette is then purified through a Qiaquick column (Qiagen, Gaithersburg, MD, USA) to eliminate nucleotides. The overhang is then generated by mixing 5 micrograms of the blunt-ended kanamycin cassette, 10 mM Tris pH 8.3, mM KC1, 2 mM MgCI 2 5 units of DNA Polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA), 20 microliters of 5 mM dTTP, in a 100 microliter reaction and incubating the reaction for 2 hours at 37 0 C. The "Kan-T" cassette is purified using a QIAquick column (Qiagen, Gaithersburg, MD. USA). The PCR product of the deletion primers (F2 and R2) is ligated to the Kan-T cassette by mixing 10 to 25 ng of deletion primer PCR product, 50 75 ng Kan-T cassette DNA, 1 microliter 1Ox T4 DNA Ligase reaction mixture, 0.5 microliter T4 DNA Ligase (New England Biolabs, Beverly, MA, USA) in a 10 microliter reaction and incubating for 16 hours at 16°C.

The ligation products are transformed into XL-1 Blue or DH5-a E.coli cells by electroporation as described previously. After recovery in SOC, cells are plated onto LB plates containing 100 microgram/ml Ampicillin and grown overnight at 37 0 C. These plates are then replica plated onto plates containing 25 microgram/ml Kanamycin and WO 98/18323 PCT/US97/19575 -84allowed to grow overnight. Resultant colonies have both the Ampicillin resistance gene present in the pT7Blue vector, and the newly introduced Kanamycin resistance gene.

Colonies are picked into LB containing 25 microgram/ml Kanamycin and plasmid DNA is isolated from the cultured cells using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD. USA).

Several tests by PCR amplification are conducted on these plasmids to verify that the Kanamycin is inserted in the H. pylori gene/ORF, and to determine the orientation of the insertion of the Kanamycin-resistance gene relative to the H. pylori gene/ORF. To verify that the Kanamycin cassette is inserted into the H. pylori sequence, the plasmid DNAs are used as templates for PCR amplification with the set of primers originally used to clone the H. pylori gene/ORFs. The correct PCR product is the size of the deleted gene/ORF but increased in size by the addition of a 1.4 kilobase Kanamycin cassette. To avoid potential polar effects of the kanamycin resistance cassette on H.

pylori gene expression, the orientation of the Kanamycin resistance gene with respect to the knock-out gene/ORF is determined and both orientations are eventually used in H.

pylori transformations (see below). To determine the orientation of insertion of the kanamycin resistance gene, primers are designed from the ends of the kanamycin resistance gene ("Kan-l" 5'-ATCTTACCTATCACCTCAAAT-3' (SEQ ID NO:207)), and "Kan-2" 5'-AGACAGCAACATCTTTGTGAA-3' (SEQ ID NO:208)). By using each of the cloning primers in conjunction with each of the Kan primers (4 combinations of primers), the orientation of the Kanamycin cassette relative to the H.pylori sequence is determined. Positive clones are classified as either in the orientation (the same direction of transcription is present for both the H. pylori gene and the Kanamycin resistance gene), or in the orientation (the direction of transcription for the H.pylori gene is opposite to that of the Kanamycin resistance gene). Clones which share the same orientation (A or B) are pooled for subsequent experiments and independently transformed into H. pylori.

Transformation ofPlasmid DNA into H. pylori cells Two strains of H. pylori are used for transformation: ATCC 55679, the clinical isolate which provided the DNA from which the H. pylori sequence database is obtained, and AH244, an isolate which had been passaged in, and has the ability to colonize the mouse stomach. Cells for transformation are grown at 37 0 C, 10% CO 2 100% humidity, either on Sheep-Blood agar plates or in Brucella Broth liquid. Cells are grown to exponential phase, and examined microscopically to determine that the cells are "healthy" (actively moving cells) and not contaminated. If grown on plates, cells are harvested by scraping cells from the plate with a sterile loop, suspended in 1 ml of WO 98/18323 PCT/US97/19575 Brucella Broth, spun down (1 minute, top speed in eppendorf microfuge) and resuspended in 200 microliters Brucella Broth. If grown in Brucella Broth liquid, cells are centrifuged (15 minutes at 3000 rpm in a Beckman TJ6 centrifuge) and the cell pellet resuspended in 200 microliters of Brucella broth. An aliquot of cells is taken to determine the optical density at 600 nm, in order to calculate the concentration of cells.

An aliquot (1 to 5 OD 600 units/25 microliter) of the resuspended cells is placed onto a prewarmed Sheep-Blood agar plate, and the plate is further incubated at 37 0 C, 6% CO 2 100% humidity for 4 hours. After this incubation, 10 microliters of plasmid DNA (100 micrograms per microliter) is spotted onto these cells. A positive control (plasmid DNA with the ribonuclease H gene disrupted by kanamycin resistance gene) and a negative control (no plasmid DNA) are done in parallel. The plates are returned to 37 0 C, 6% CO 2 for an additional 4 hours of incubation. Cells are then spread onto that plate using a swab wetted in Brucella broth, and grown for 20 hours at 37 0 C, 6% CO2. Cells are then transferred to a Sheep-Blood agar plate containing 25 micrograms/ml Kanamycin, and allowed to grow for 3 to 5 days at 37 0 C, 6% CO 2 100% humidity. If colonies appear, they are picked and regrown as patches on a fresh Sheep-Blood agar plate containing micrograms/ml Kanamycin.

Three sets of PCR tests are done to verify that the colonies of transformants have arisen from homologous recombination at the proper chromosomal location. The template for PCR (DNA from the colony) is obtained by a rapid boiling DNA preparation method as follows. An aliquot of the colony (stab of the colony with a toothpick) is introduced into 100 microliters of 1% Triton X-100, 20 mM Tris, pH and boiled for 6 minutes. An equal volume of phenol: chloroform is added and vortexed. The mixture is microfuged for 5 minutes and the supernatant is used as DNA template for PCR with combinations of the following primers to verify homologous recombination at the proper chromosomal location.

TEST 1. PCR with cloning primers originally used to amplify the gene/ORF. A positive result of homologous recombination at the correct chromosomal location should show a single PCR product whose size is expected to be the size of the deleted gene/ORF but increased in size by the addition of a 1.4 kilobase Kanamycin cassette. A PCR product of just the size of the gene/ORF is proof that the gene had not been knocked out and that the transformant is not the result of homologous recombination at the correct chromosome location.

TEST 2. PCR with F3 (primer designed from sequences upstream of the gene/ORF and not present on the plasmid), and either primer Kan-1 or Kan-2 (primers designed from the ends of the kanamycin resistance gene), depending on whether the plasmid DNA used was of or orientation. Homologous recombination at the WO 98/18323 PCT/US97/19575 -86correct chromosomal location will result in a single PCR product of the expected size from the location of F3 to the insertion site of kanamycin resistance gene). No PCR product or PCR product(s) of incorrect size(s) will prove that the plasmid had not integrated at the correct site and that the gene had not been knocked out.

TEST 3. PCR with R3 (primer designed from sequences downstream of the gene/ORF and not present on the plasmid) and either primer Kan-1 or Kan-2, depending on whether the plasmid DNA used was of or orientation. Homologous recombination at the correct chromosomal location will result in a single PCR product of the expected size from the insertion site of kanamycin resistance gene to the downstream location of R3). Again, no PCR product or PCR product(s) of incorrect size(s) will prove that the plasmid had not integrated at the correct site and that the gene had not been knocked out.

Transformants showing positive results for all three tests above indicate that the gene is not essential for survival in vitro.

A negative result in any of the three above tests for each transformant indicates that the gene had not been disrupted, and that the gene is essential for survival in vitro.

In the event that no colonies result from two independent transformations while the positive control with the disrupted ribonuclease H plasmid DNA produces transformants, the plasmid DNA is further analyzed by PCR on DNA from transformant populations prior to plating for colony formation. This will verify that the plasmid can enter the cells and undergo homologous recombination at the correct site. Briefly, plasmid DNA is incubated according to the transformation protocol described above.

DNA is extracted from the H. pylori cells immediately after incubation with the plasmid DNAs and the DNA is used as template for the above TEST 2 and TEST 3. Positive results in TEST 2 and TEST 3 would verify that the plasmid DNA could enter the cells and undergo homologous recombination at the correct chromosomal location. If TEST 2 and TEST 3 are positive, then failure to obtain viable transformants indicates that the gene is essential, and cells suffering a disruption in that gene are incapable of colony formation VII. High-throughput drug screen assay Cloning, expression and protein purification Cloning, transformation, expression and purification of the H. pylori target gene and its protein product,e.g., an H. pylori enzyme, to be used in a high-throughput drug screen assay, is carried out essentially as described in Examples II and III above.

Development and application of a screening assay for a particular H. pylori gene product, peptidyl-propyl cis-trans isomerase. is described below as a specific example.

-87- Enzymatic Assay The assay is essentially as described by Fisher (Fischer, et.al. (1984) Biomed.

Biochim. Acta 43:1101-1111). The assay measures the cis-trans isomerization of the Ala-Pro bond in the test peptide N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (Sigma S- 7388, lot 84H5805). The assay is coupled with c-chymotrypsin, where the ability of the protease to cleave the test peptide occurs only when the Ala-Pro bond is in trans.

The conversion of the test peptide to the trans isomer in the assay is followed at 390 nm on a Beckman Model DU-650 spectophotometer. The data are.collected every second with an average scanning of time of 0.5 second. Assays are carried out in 35 mM Hepes, pH 8.0, in a final volume of 400 ul, with 10 NM cx-chymotrypsin (type 1-5 from bovine Pancreas. Sigma C-7762, lot 23H7020) and 10 nM PPIase. To initiate the reaction. 10 pl of the substrate 2 mM N-Succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in DMSO) is added to 390 p.1 of reaction mixture at room temperature.

Enzymatic assay in crude bacterial extract.

A 50 ml culture of Helicobacter pylori (strain J99) in Brucella broth is harvested at mid-log phase (OD 600 nm 1) and resuspended in lysis buffer with the following S protease inhibitors: 1 mM PMSF, and 10 p.g/ml of each of aprotinin, leupeptin, pepstatine, TLCK, TPCK, and soybean trypsin inhibitor. The suspension is subjected to 20 3 cycles of freeze-thaw (15 minutes at -70 O C, then 30 minutes at room temperature), followed by sonication (three 20 second bursts). The lysate is centrifuged (12,000 g x 30 minutes) and the supernatant is assayed for enzymatic activity as described above.

Many H. pylori enzymes can be expressed at high levels and in an active form in E. coli. Such high yields of purified proteins provide for the design of various high throughput drug screening assays.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments and methods described herein. Such equivalents are intended to be encompassed by the scope of the following claims.

With reference to the'use of the word(s) "ccmprise" or "ccrprises" or "ccrpri.sing" in the foregoing description and/or in the following claims, %e note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted incl usively, cather than exclusiveiy, and 4111 that we intend each of those wds to be so intrpreted in const ng the foregoing description and/or the following claims.

WO 98/18323 PCT/US97/19575 -88- SEQUENCE LISTING 1) GENERAL INFORMATION:

APPLICANT:

NAME: Astra Aktiebolag STREET: S-151 CITY: Sodertalje

STATE:

COUNTRY: Sweden POSTAL CODE (ZIP) (ii) TITLE OF INVENTION: NUCLEIC ACID AND AMINO ACID SEQUENCES RELATING TO HELICOBACTER PYLORI AND VACCINE COMPOSITIONS THEREOF (iii) NUMBER OF SEQUENCES: 208 (iv) COMPUTER READABLE FORM: MEDIUM TYPE:

COMPUTER:

OPERATING SYSTEM:

SOFTWARE:

CURRENT APPLICATION DATA: APPLICATION NUMBER FILING DATE: (vi) PRIOR APPLICATION DATA: APPLICATION NUMBER:US 08/739,150 FILING DATE: 28-OCT-1996 (vii) PRIOR APPLICATION DATA: APPLICATION NUMBER: US 08/759,739 FILING DATE: 06-DEC-1996 (viii) PRIOR APPLICATION DATA: APPLICATION NUMBER: US 08/891,928 FILING DATE: 14-JULY-1997 (ix) CORRESPONDENCE ADDRESS: ADDRESSEE: LAHIVE COCKFIELD STREET: 28 State Street CITY: Boston STATE: Massachusetts COUNTRY: USA ZIP: 02109-1875 ATTORNEY/AGENT INFORMATION: NAME: Mandragouras, Amy E.

REGISTRATION NUMBER: 36,207 REFERENCE/DOCKET NUMBER: GTN-001CP10PC WO 98/18323 PCT/US97/19575 -89- (xi) TELECOMMUNICATION INFORMATION: TELEPHONE: (617)227-7400 TELEFAX: (617)742-4214 INFORMATION FOR SEQ ID NO:1: SEQUENCE CHARACTERISTICS: LENGTH: 561 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...561 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:

ATGATTAAAA

GTGAATGGGT

AATTACTCTG

GTAGGCTTTG

ACTTCAGGGA

ATTGTCAATC

GCCGGAAACA

AATTTAGGCG

CCTATGGTTA

GAATTGCTTG

TTTTCATGGG

ATTGGCGTCA

CCAATAAATG

CTGAACACAC

TCATTCCTTT

CTTGGATGTT

GAAGAATGCG

ATCAGGGTAG

TATTTTAAGC

TGCGGGTTAT

TGGCAATGAC

GTTTGGGGCT

CAAAACCAAT

GGATAAATTC

CCCTTATGAT

TGTTGGGGAT

CAAAGATGTA

TTGAGCGCGA

CAACAAGGTC

CTTTATGGTT

AGGGTGTATG

TTGCTCACCT

GCTCTAGGTC

GTCAATCAAA

CGCAGTGCGT

GGGCTTATCC

GTTTAGCGTT

GTTATGGCCC

TGAATTTCAA

GCTTTTTAGA

ATGGCGGCGG

TCATTGGTGG

CCAGATTCCA

TTGAAGCGGG

GCTACTATTC

AGCTGGCGAA

TTATAACAGC

ATTAGGTTTT

TTGGTTTAAC

TGGCGATTTG

CGTTCAATTA

GTTCTTATGG

CGTGAAATTC

TTGGTATGTG

GATTATGTCT TCACTTTCTA G INFORMATION FOR SEQ ID NO:2: SEQUENCE CHARACTERISTICS: LENGTH: 351 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 WO 9818323PCTIUS97/19575 90 (ix) FEATURE: NAME/KEY: misc feature LOCATION .351 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: 5

TTGATGCGCA

CTCGCTTCTT

GCTATAGGGA

GACCCAGAAA

ATCTTACAAG

GAGAGCAGGC

TTATCATAAG

TGATGGGGGG

TTTTTGTGTT

AACGAGAAGA

ACAAGCAAAA

AAAAACAAGA

GTTACTTTCA

GCTTTGGTAT

GATCTTGTTT

ATACATAGAA

AGAAGAGCAA

CCTTAAAGAA

TTTAAAATGA

GCTTTCAATG

GTTTTTTTTA

CGGCTTAAAPA

ATGCGCCTCT

CAAATGAAAA

ACGCTTTTTT

GCGAAGGCTC

TCCGCCCTGT

AAAACCATGA

ATCAAGCCAA

AATACTCATA

AAAACTCGCG

TGAGATTGTC

GAGTTTCCAA

GAGGAAAATG

AAAAGAGCGA

A

120 180 240 300 351 INFORMATION FOR SEQ ID NO:3: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1038 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...1038 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:

ATGGTTAAAC

CTGTTTTTTA

AAAGTGAGCT

TTTATTTTGC

GACCATGAAT

TTTGTGCCTT

CCCACTTCTA

AACATCAGAG

ACTGAAAACA

AGCTTTATTT

TTGTATAACG

GAATTGCATT

GGCACGGATT

AAACGCCGTT

ATCCCCTTAT

CTTGGAGCGG

ATGACCTTTT

ATTTTAAAGC

ACTATCTTTT

TCTCTTCCAT

TTTTGGATCT

CGATCACTTT

TGTTAGTGTT

TAAGTTTGTT

AGAGCGCTTA

CGGGTGAATT

ATTCCTATGA

TGGCTCAAAA

GGCATGCGTA

TGCGCAACAA

ATTTGGGTTA

TTTCTCAAGC

TTGGCATCGC

TTGGGGTTTA

TCTTCCCCTT

GTTATTAA

CATGGCGGTT

TGTGTTATTA

GGTGCAACTC

TTTTGCGGCT

TTTCTCTTTA

AGTGAGCGCG

TTACGGGTTT

CGGGCAAAAA

TAATTTGGTG

AGGCAATATC

TTTCACTCAA

GCTCAAGTCT

TTGGAAAAAA

GATCTTAGTT

CAACCCGCGA

TTTTTTAATG

TATTTGGGCG

TCGCAGGTCT

ATCAGTATTG

TTTTTGTATT

TGCGCTTTGG

GGGGTTTCGC

ATTTTATTAG

TTGCGTCAAA

TTAGGCGATT

CTTTTTTCTA

AACAATCAAA

GGCGATAAAA

TTCAA.TTCTA

GCCTTTGGTA

TCCTTGTTCC

TTCAAAACGA

GTGCATGTGA

TTTATTTCTT

TTTTCTCCTT

CAAGCGTAAC

'CCTTGCCAGG

GGCTTTCAAG

CTAAAAAAAT

CGTTTTCGCT

AAAAAGACAA

GGCTCGTGTA

ATAAAAGTCT

ACGGCGTGTT

TGCGTAAGGT

ATGATGCGGC

AAAACGCTAA

CTTTAGCGAG

ATTGGAGTTA

TTTCTACGGA

ATTTATTGTT

CTTTTTAGTG

GCTCGTGATT

AACCATTTTT

GCTTAGCTAT

GACTAAAGCG

CATCTTAATC

GATTGACATT

TGTGGATAAG

CTCTCAAGAA

TGAATTGAAT

TGATTTTGAA

TTATTTGCAA

TAAAAATCAA

CGTGTTTTTA

TTTCTATGTC

TTTGTTTTTG

TAGAAAATTC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1038 WO 98/18323 PCTIUS97/19575 -91 INFORMATION FOR SEQ ID NO:4: SEQUENCE CHARACTERISTICS: LENGTH: 831 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 831 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:

ATGAAGAAAA

GCGGTCTTTT

AAACAAAACC

ATAACCGCCT

GTGCGTTATG

GGCGAGGGCT

ATCATTTTCC

GCTAGCGGGA

GACAACCCCA

TTGTCAATGT

ATTTTCATGT

TCCAACTTAG

GATATGACCT

CGCTACATCA

AAGCAAAAGT

TTTTGTTGAG

ATAAGATTTT

CAGGGAATGC

ACACCAAGAC

TGCTCGTTAA

CCTTTTATGT

AGGATCAAAA

TTTGGCATGT

GGAATCCTAA

CCACGAGCAA

ACGGCTTTAT

TTACCCCACA

ACTCTAAGAC

CTTTTGGTGT

CGTATCAGAC

TGAAATCCTT

GATCCTATTG

TAAAGAAGCG

AACCGATTAT

CCAAGACAGC

ATATAAGATT

CAATGCGACT

GATTTATGTC

TAAAAGAACT

TTATTTGCAA

AATCCGTTAC

GCAGGTTTTT

TGTTTTAAAA

GCTAAAGAAA

GCGGATAAAG

AATTATGACG

TTATTAGAAG

GTGAAATTGA

GTGAGCGGGA

AAAAACATGA

TCAGGCTCAT

GGCGATATTC

ACCGGGTTTT

CCCTTTTATT

AAAAGGGGTT

ATTCAATGCG

TGATTCGTTG

TCGCTATGCA

TGAGCGCCAA

TGTATATTCT

GCAATATTAA

GTTTGAACGA

TTTGGGTGAG

GCGCTTCAGG

TTAACATGCA

CTGTATTGTA

TATACCCTGA

TAGCCCCCAA

TTGGCTTGAA

CGCTATTTTA

GTTGTATTTG

ACGATTTGAC

AGACAATGTG

AGCGGATAAG

GGTTTATAGG

AAAATATGAG

CGCGGATATT

GTGCAGCATT

AAAATCGCAT

TTTGCCCTAT

GTTTGGCACT

AAACTCATGG

TTTTGAAGCG

G

120 180 240 300 360 420 480 540 600 660 720 780 831 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 675 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 WO 9818323PCTIUS97/19575 92 (ix) FEATURE: NAME/KEY: misc feature LOCATION .675 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGATTAGAT

CTAGGTGCTA

CGAGTAAAAC

GGCTCTCAAT

GAAAAGATTT

AAAGAAGACA

GCTAAAGTTT

CCAAATAAAA

TTTATTGATG

CTTGGCATTA

TTAGACAATA

CTATGGCTAG

TAAAAGGTTT

CTGCTCCCTT

TACACAATAT

ACTTGAATAG

TTGAATGCGT

CTAAAGATAA

TAAGGCAAAA

AGCAACTTCA

ATTGGCACGA

AAGAATATAG

TAAAAAAGAT

TATGA

GAATAAAACT

AATGGCAAAG

CAAAGAAGAT

TGGTTGGAAT

AGAAGAAGAA

AGAAGAACTT

ATTTATGGCT

AACCATGCTT

ACGCTTTGGG

TGATGAAGGA

TTTGAAGAAA

TTAAAAACAA GCTTATTAGC CCTTTATTAA GCGATGAAGA ACGCTGACTA GCTGTAATGC TTATCTAAAG AATTTCCGCA AAACATAAAC AAGCCCTTAA GCAAAAAAAA TCAAAGAAAT TTTGAAATGA AAGAACACTC GAGAACGCTT TTGATAATGG GGTATAAGTA GAGAGAATAC AAGATATTGC CTTTGGCGAA GCACTTATGA TACTAGACAA

TGGGGTTTTA

CTTATTGAAA

TAAGGTGGAC

AGAATATAGA

TTTAATCAAT

TAAAGAAAAA

TAAAGAATTC

AGCTGAAAGT

TTATAAAGCA

AGAAGTTATA

CCCTTATCTG

INFORMATION FOR SEQ ID NO:6: SEQUENCE CHARACTERISTICS: LENGTH: 1290 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1290 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:

ATGCCATACG

TGTATGATAA

CAAATCATTA

CAAATCTTTT

TATTACAAGG

AAAGAAAGCT

CGTTATGCGA

TTCAATATCC

AAAGAAATTG

GAAAATTTGC

ACGCAATTAG

GATTATAAAG

GAATACGATG

CCTTAAGAA-A

ATTTGCATGC

AGACAGAGCC

CTTTTGTATC

ACATCTTAAA

ATGAGCCTAA

TTTTAGTGAT

AAGTCTTTGA

AAAAAGAAAA

TCCAAAATAC

AAAATCATAC

AGCAATTAGG

ATGATGGCCT

AAGATTTTTC

CAAAAGCTAT

TTGCTCTTTG

CCAATACGAT

CAAACTCAAC

GATTGAATTA

GAACACCCTT

CAGCGATGAA

ATTCCCTTTT

GACTATCAAT

CGAGCTTTCT

CATGCTCGCA

GATAGGTGAA

AAACGCCTTT

CTGTTTTCTC

GAGTGCTTGA

GATAACAACC

CCCGTATTCA

GCGATTTTAC

TTAGCGTATT

GAAAGCCCTG

ATCATCGCTT

ACCCCTACTT

TTAAGCGAGC

ACTTTCATTA

CGCTTGAGGC

TATTGTTTTT

CTTTGCCCCC

AAGACTTGAT

AAGATGAGAG

TCGCTTCTCA

TGCCTAAAAA

TGAACACCAG

AAAAATTAGA

TATTGACTAA

ATGTGCCTAC

GCTTGTATTT

GCCCTAATTC

AAATCACGGA

TTTAATTGTT

AGCGCACCAG

GCTGCAAAAT

CCTTAAAACT

AACTCCAGCT

GGTGGTGGGC

AAACAACGAT

AGAAACCTAT

AGAGGGCGTG

GGTGAATAAA

TGGGGGGATT

GCCCGTGATT

GTCTTTAAAC

WO 98/18323 WO 9818323PCT[US97/19575 93

GTTGAAGTCA

TTTAGAAAAC

AAAAGCGGTC

TCCACACAAA

AATTTATTCA

TTATTAGAGA

ATGTTTTTAA

AATCAAGTCC

AAAAACGAAA

AACACCAAGA.

ATGATGCGTT

TGATCCTTTC

TCAATTTCAA

TTGTCAATGC

GCGATTTAAG

ACACGCTAGA

GTTACCACAA

GCGAAACAAA

AAACATTTCT

TTTTAAAAAT

TCAAATAGGG

CCCCTCTTTA

CTTGCAAAAC

GCATGATTGG

TCCGCATTTT

TCAAATTTAT

AAAAGAATAA

TACAAACAAG

TCTACCTTAA

CTTTTAGAGT

CTCTTGCTCA

AGCGATGAAA

GTGAATTATT

AAAAAGTCTT

CAGGCTTTAG

CGACCAGTTT

TTTTGAACAC

ATAAGCCTCT

CCCAGCCTAA

CGCTGATAGA

CCAGCGCGAT

TTCAAGAGAG

GGTATTCTTT

TTCTAAAAAT

CCCTACCACT

TAAAATCCTT

AGACAGGAAA

ATACGCTTCC

AGGGCTAGAG

TTTGGAAGAC

TGAGCCGATA

840 900 960 1020 1080 1140 1200 1260 1290 INFORMATION FOR SEQ ID NO:7: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1368 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1368 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:

GTGTTAAAAT

TTATTGGCTT

AACCATTCCA

ACGATCAAGC

AAAATAGGCG

GACCAAGCCA

GGGTTTTTAG

AATTATGTGC

TTAGGGCGTT

GATTATAAAA

GCTTTTGGGC

GAAGTTTATG

ATGCCTTTTG

GATAGCAACC

TTCCCTGTTT

TGGGGCGCAT

GGTTATTACC

CCTTTTAATT

GACGCCGTTT

TTAGGCAGAT

TATAAATGGG

CACAACGGCT

TTCAAAAATT

TTGATTATAA

AACTCAATTC

TTCAAGTGGA

TTGGGGGGAT

CGCATCAAAT

GCAACGCTCC

TGTATAATTC

ATCTCTCTAA

TCAATTCTAA

AATGGATACG

ATGGCATCCA

CTTATTTTTC

CGAAATTCAA

ATGCTAAAGA

CGCTTTTGAT

AAAATTTTGG

ATAGAAATAA

CTGGGTATGT

ACACTTATGC

GTTCTTTTGC

ATAGATTAGA

ACCCTTATTG

GTTTAGTGGG

CAAAGAAGGG

TTCCAATCTG

TTTAGGAGCG

CTATGGCTCA

TTGGAAAGAC

CTATCTGTTT

CATGGATTTT

AATAGCGTTA

GGATTGGTAT

TGCCGCGCA.A

GCCTAAGATT

AGGCTTAGGG

TTTATACGAT

CCACCAACGC

CAACGCTAAC

CAGCGTTTAT

CTTTGGTGGG

CACTAGAGCG

TAGAGTTGAT

CTATCTCACC

TTTGTTTCCA

GTAGCGGAAT

ATTTTCCCTA

CTCCCTAAAA

CTCGCTTACG

GAACTTTTTT

TCCCTCATAG

TATTCTTATG

ATGAGTTCCT

AAATGGTTTA

GCCCCTATTG

CTCTATTTTT

TACGGAGCGC

TTAAGGGCTC

GTGTATTGGC

TTTGACTACA

GCAAGGATTG

GGTGGGGTCT

GGGGTGTATA

AGCGAAAGAT

GTGAATTTAG

GGCCCTTTCA

TTCTTTATAA

CTGTTTCTAA

CAGCCACCTT

ACATTGAAAA

ATTCCACCAA

ACCTCATAGG

AATCTGACGC

GCGATAAATT

ACACACAGGG

GCTCTTTTGG

TAACTGAAGA

CTAGCAAGCA

CCGGTGTTAA.

AAACCACTAT

GTAACTCTAA

ACGAATTTAA

GCTGGTATGG

TCAGTAACGC

GAGGGTTTTT

CCATCAACTT

AATACTATGT

ACAAAGCCTT

TCAAAGCCCT

AGTGGGGTTT

TGTAACCGCC

ACACAGCTTA

AACGCTCATA

GCGTTGGTGG

TCACACCCGT

CCACCTAAAA

TTTTGAACTG

GAGGGCGTTG

TGGCAGAAAA

TGTTCAAGTC

AATCCATATT

TAATGTGATT

GATTGGCGAG

CTTTGGCTTT

TAACCCCATC

TATTACCGCA

ATGGGGTATT

GAACTTGGGC

GGTCAGCATG

TAAGGCTGAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 WO 98/18323 WO 9818323PCTIUS97/19575 94 GCACAAGATA GGAGTAACCT TATGGTTAGC ATGAAATTCT TTTTTTAA INFORMATION FOR SEQ ID NO:8: SEQUENCE CHARACTERISTICS: LENGTH: 849 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .849 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: 1368

ATGGGGTGTT

GGGCTTTCAA

AATGACGCCA

CATGTTACGC

CATGTTGTAG

GATAAGTTTC

CAAGTGTTGC

TCCGTTTTGG

GATCCCAATA

AATTTTTATG

TTTCAGGCAA.

TCAAAAAGCG

TTAAACAGAA

ATCGCCAAAT

AAAAAGTAG

CGTTTATCTT

GCGTGTTGAT

AAAACCAACA

CACTAGATTT

GTATTTTAAT

AAGACGCTTT

GTTTTCAAGA.

ATTTGAAAGG

GTCCCAATTT

AACCAGAAAG,

TAACATACAC

TTATCCATGA

TGTA.TGCGGT

ACAGAGACGC

TAAAAAAGTT

CGGTTGCGCG

ACCAGTTCAA

TAATTACCCG

GCCACGCATT

AATTAATCAA

TGAAAAAGCT

GTGGGTAGGA

AGACACGCTA

CAATCGTGTC

ATACACCTCT

AAATTTGGAT

TGTCATGAAA

TATTGATAGA.

AGGGTTTATT

ATGAATCCAA

ACTCATGAAA

GTGCATATTG

CAAGTGAGCG

ATCCAAACTA

TTGAATGTGC

ATCTTAGAAG

GTGGATCAAA

GTCCATGATT

ACTAATAACG

AAGAATAGAG

AAAGCTGTAA

ATGAAAGGCT

CTAAAATGTT

GCGCTGAGAC

GAATGACAAC

TTCAAGCCCC

ATAATCTAAA

TTTTTGAAAA

AAGATAAGAA

ATTTGAAAAT

GCTCAGGCTC

TTGCTGTAGA

CTTCAGGAGG

AAGACGCGAT

CAGAACTTAC

TTAAAAGTTC

GGTTGCTTTG

AAAAAAACCA

AAGTTCTGAA

ACAAAACCAT

ACCCTATATT

AAGAGGCTAT

AAAGATTTTT

GAATTTAAAA

TGTATGGTTT

AGTAGGAACT

GTTTAATTCT

ACACAAGATT

AAAAGAAAAT

TATGCCTCAA

120 180 240 300 360 420 480 540 600 660 720 780 840 849 INFORMATION FOR SEQ ID NO:9: SEQUENCE CHARACTERISTICS: LENGTH: 843 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/18323 95 (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .843 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: PCTIUS97/19575

ATGAAACTGA

TGCAGTAACT

AATGAACTGA

TTCATGGTGC

GTACTAACTT

AAGATCCTCC

TACTTGCAAC

AATCCCAACA

CTAGGAGCTA

GTGATCAATG

ACTCTCTTGC

TTAGAAACAT

ATTTTTAAGA

CAAGAAGAAA

TGA

GAGCAAGTGT

ATGCGAAAAA

TAGAGAAGTA

AAGTGAAGTT

TCAAACTTGT

AATACAAGAA

CCACTTTGAA

ACAAAGAAAA~

ACACAAAAAA

AAGTGGCA.AG

AAGACAAGGA

TGAGTAATCG

ATGGCAACTT

GAGAGAATGA

TTTAATCGGT

AGTGGTGAAA

TAGTGAGATC

GCCAAATTAC

TCACCATTCT

TTACTTCCAA

TCAAAAGGGT

ACCACAGACC

CTTGCATGGC

AGAAAAAGCT

ACAAGAATAT

TGCAGGTTAT

GAACATGCAA

ATACTTGCGC

GTGGCAATTC

CAAAAGAACC

CCCTTAAATG

AAGGACTATT

AAAAAGATTA

GCTAACGGGG

GTGGTGATGA

TTTGATGTGT

TATGATGTGA

CAGCTAGAAA

ACCACTAGGA

CAAATGAGGC

GCCAAAGAAG

AATCAAATCA

TGTGCTTAAT

ATGTTTATAC

ACAAACTCAA

TGTTGGATAA.

CGCTCATAGG

CAAGATCTGA

TAGCGAGTAA

TGCAAGGAAG

GTGGAGCAAA

AAATCAATCA

AAAATAACCA

AGAATGTGAT

AAGAAGTTAG

GAAGTTTGCT

TTTAAGTGCG

GCCTGTGTAT

AGACACACCA

TAAACAAGTT

CGATGCCAAT

CATTGATTTT

CTACAATGAT

TCAGCCAATG

CAACAAGCAA

GTATTACAAG

ACGAGAAATT

TAGTTCTGAG

GGAGAAGCTA

CAGTGGTAAG

120 180 240 300 360 420 480 540 600 660 720 780 840 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1179 base pairs TYPE: nucleic acid STRANflEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1179 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAGAAAAC

GGCTTTTTCA

AAAAGACACA

ATTTTAAAAA

TCATCTTTAT

TTCTTGCCTT

ATCGATCTAG

TATTCATCCC

TAGAAGCCGG

CCACCACAAA

GAGCGGCTAA

CCCCTGTTAG

ATAATTTAAA

GCGTGATAGA

ACTTTTATTA

CTTTGAAACT

AAACACTTAC

TTTATTCACC

AGTGTTGTA.T

TAATGTTAAG

GACTATCCCC

TTCAGCGC'TT

GGGCTATTAG

GCAACTTACA

AATGCCGAAG

ATGTATAATG

CTTAGTTTTA

AAACACTCTA

TAGAAGCGAA

AAGGCACACA

ATTATTTACC

CGATTTCAAA

GTCAATTAAC

CAGACGCTCA

AGATTGTTTT

CGAGAAAAAC

AACGCAAGAA

CACAGACACG

ATTAAAATTC

TATAGAAAAC

AGGCAATGTG

GCCCGGAGAG

WO 98/18323 WO 9818323PCTIUS97/19575 96

GCATTTGATA

AGCACTTCTA

ACAAATTTGG

GAAGCCTTTA

GTTTTAGACT

AGCCCAACAG

GTCAATTCTA

AAAAACAAAG

AGTGATATTA

GCTTCTGCTT

GATTTAAGAA

ATGACCTATC

AAGCCAAAAG

GTCTAAAAAT

TTTCTGACGd

TCGTAAATTA

CCCCACAAAC

CCCAATCTTG

ATTGCGATAA

AAGTCGATCA

CGGATCTTGA

CCCCTAGCAA

TAGATCCTAA

CCATCTTGCA

AAAGAGTGCC

ATTCTGATGG

TGACCCCTAT

TAACACGCAG

TAGGAATGAA

CGCAGAAGAA

GGGCGATGCG

TGATCCTTCA

AAAATATGTG

TGTAA TTGTT

CAATGATGAT

AAAACTCTTT

TGAATTCAGC

GGTAACGAAA

CCTCCCCTAT

ACTTTATTTC

AGGGTGTTTG

AACAAATTTA

TTCACTAATT

ATCTTAAACG

AAATGCGTAA

TTAAACAAAC

TTAAAdGATT

GGCAAGCATT

GGCGATAACC

CACACTAAAG

GATGGTCAAG

AATGTGTGT

TTCCAAAAAT

AAACGCTCAA

AAGATCACGA

TAATGTTGAA

CTCCTTTTGA

ATCCTGGGAC

AAGACATTGT

CAGGGGTTGT

ATGGCCAGTT

TTAAGACTAT

GCTATGGGCA

TGGAAAAGGA

TGAAGCCACT

TAAGATTAAG

AAATCATTGG

CATGATCGCT

GTTCACTAAC

AAACGGGCTT

CAATAAATTT

AGGGCTTGGG

AGGGGTAGTA

CAATTTAGAG

TAACGGGAAT

TAGTAATGGC

480 540 600 660 720 780 840 900 960 1020 1080 1140 1179 INFORMATION FOR SEQ ID NO:11: SEQUENCE CHARACTERISTICS: LENGTH: 813 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular.

(ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .813 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:

ATGAAAAAGT

GAAGGTGATG

AATATTTATA

GCTAATAAGC

GCTTTGAATG

GATATGACAA

GATTTAGGTA

GTGGGGAGCG

GGTGGGGTCG

CAAATCATTG

CCTTATAGCA

GCCAATATCT

AAATTTTTGA

TCGCTTTATT

TTGTAGCTTT

GTGTTTATAT

ATACAGGGGA

ATAATCCAGG

GTTTTGGGTT

GCAAGTGGTT

AACAAGTTTA

ATTTGTTAGC

CTATCGGCGG

AAGCCAAAGG

CCAACACTTC

ACAAGCATAA

GCGCGGGTCC

TGGGGTATAA

AGGGCTTCTA

AGGGACTAAT

TTGCACAGGG

AGGCACCAAT

GAATGTGGGT

TGGTTTTAGA

TGCACCTAAT

TGATATTATT

TAACACTTGG

TCCTGATGTT

AACCGTCGCT

TGGCGTGGAA

TAACGCTACT

CTACACTTTT

TCCGCGGTTT

TATCAGCTTG

AGTGTTGTAG

ATCAATTGGC

TATAAGAAAT

GTGTATGGGC

AAAATCCAGT

GATAAAGACA

AAAAGCTCTG

TGTACCCCTA

TTTCAAGTGT

TTTGGCGTGA

AACCTTTATT

TAA

TAAGCTCTTC

GACAAGCCCG

GTTGCCCCCC

ACTCCAAATA

TCTTCCAATT

TTTTTGATTA

TGGATATGGT

ACGCTTCTTT

CAGCAAACTA

CTTATTGTAA

GGTTGAATTT

GAGTGCCGCT

ACCATTTGAA

GTTGTTAGCC

TTTGAATAGC

AGGTCTTACC

CGCTAATGGG

CAAGTCGCTA

CGGGCATGCC

CTCTTGGGGT

TGGTATTTTT

TTGGAAAGAG

CCCTAATGCC

TGGGGTGAGA

ACTCATCAAT

ACGGGATTAT

120 180 240 300 360 420 480 540 600 660 720 780 813 INFORMATION FOR SEQ ID NO:12: SEQUENCE CHARACTERISTICS: WO 98/18323 PCT/US97/19575 -97- LENGTH: 423 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...423 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:

ATGCATCCTA

GGAACACTTT

GCAAAGAGTT

GAATTAATAG

GACATGAGAG

GAAATTGATT

ATAGAAAAAT

TAA

TAATGTTTGC

GCATGGCGTT

TGATAGGCAA

AATGTGGCGT

CCAGACAAGT

TAAAAAAGAT

CCTCAATGAT

CTATATCGCT AACGCGCTCG TCAAAAAATA TCTCAAGTCA CCTTTCTCAA GTGATTATCT CCCATTAAGC GATAGTGAAA GCTAGTAAAA AATATCGTTA TTGCAAGAAC TACTTTATAT CTTAAAAAAG CAAACCAAGA CTCAAGCTAG AAAGATCAAC AAGAATTAGG CATTGATAAA ACCCCACAAA AGATACTGAT TCAATTTCTT ACACAACACG CAAACGCTTC AGCTTTTATT TCTTGATAGC AATGCTGGTA AACTTATAAG GAAGAGTATT INFORMATION FOR SEQ ID NO:13: SEQUENCE CHARACTERISTICS: LENGTH: 771 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...771 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: ATGTTGGGGA GCGTCAAAAA AGCGGTTTTT AGGGTTTTGT GTTTGGGGGC GTTGTGTTTA TGCGGGGGGT TAATGGCAGA GCAAGATCCT AAAGAGCTTA TATTTTCAGG TATAACTATT TACACGGATA AAAATTTCAC TAGAGCTAAG AAATATTTTG AAAAAGCTTG CAAATCAAAC 120 180 WO'98/18323 WO 9818323PCT/US97/19575 98

GATGCTGATG

GAAAACGCAA

AAATTAAACG

CTTAAAAATG,

ATGCTGTCAG

CTAGAATATT

GGGGATTATT

GCCAAAGCTT

GAGGGTAAAG

AAGCTAGGAT

GCTGTGCAAT

GAGAGAGCAT

ATGCTGAAAA

CTTTAGAATA

CAACTTTTTA

ATTCTAAAGC

TTTTTGGTGA

GTGAGTTGAA

GCGTGGCAAA

TAAAAGAAGC

CTTAAGAGAG

TGAAAAAGCT

ATGCAAGGAC

TTACTCTAAA

TAACGATATG

TTGCGAGTTA

AGGCGTAACA

CGATGCTAAA

GGATGAAAAG

ATGCGATATT

GTTTATTCTA

CTTGAACACA

TTAGCAGAGT

TCTTGTAAGT

ATAAAGGGTT

AATAACGGTG

AAAGATTTCA

GGGTGTTACG

CAAACGACAG

CTCAAAGAAC

GTGGTAAAGC

CCGCTACTGC

TTTATTTTAA

TAAATAATGT

TGAAAAAAGA

GAGGGTGTTC

AAAAAGCTTT

CTCTAGCAGC

AAAACCTTGA

AAAAACAATA

CATAGCGAGA

TAAAGTTTGT

TGTAAACGAT

TGAAGGGTGT

TAAAAAAGAT

TAAATTAGGA

TGAATATTCT

GTTTTATAAT

AAAGAGTTGC

A

INFORMATION FOR SEQ ID NO:14: SEQUENCE CHARACTERISTICS: LENGTH: 729 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii.) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .729 (xi) SEQUENCE DESCRIPTION: SEQ ID WO:14:

ATGAAAAAAT

GGCATGGATG

CATGCGGATA

CTCTTGGGGT

GACTACGCTC

CAAGTGGCTA

CCCAGAACTT

GTCATCAATA

TCATGGCTTA

AAGAAAGCCA

CATTCTAGCA

GCAAAAAATT

ACTTTCTAG

TTTTTTCTCA

GTAATGGCGT

TTAATTCTCA

ATCAATTTTT

ATGCCAATTC

GTCAAATTCT

TTGAGCCGAA

ACGGCATCAT

TGGCGACACC

CTTCTTTCCA

TTGAAGCGGG

TGGATATAGG

ATCTTTGTTA

TTTTTTAGGG

AAAACAAGCC

CTTTGAAAAA

TATTAAGCTT

TGGGAAACAA

CATGCTCACT

GAGTTTGGGG

GAGCTTTGAG

ATTTTTATTC

CGTGAAATTC

GTTTAGGCGC

GCTCTTATTA

GCGGGTTATT

ACCAACGCTA

CACTTTGGCT

AAAAACCCTA

GAAATCAATC

TATGGGGGGG

GCTTTTGGCG

GGCATTTTAG

AATGTGGGGG

CCCATGCTAA

GTGTATTCGT

TCTCTATGAA

TGCAAGGACA

CGATCAAAGG

TACGCCTTTA

ACTATAATAG

GTTTAACAAA

CTATGGACGT

GGATACAATT

TGGAACAAGC

CTCGCTTAAG

AGAAAAACCC

GGTATGTGAA

TGCGGTATCT

GGCGCAAATG

CTTTGACGCG

TGGGTTTTTT

CGAAGCGGCG

CATTGCCGAT

GATGGTTAAT

GGCCGGCAAT

CCTTGTGAGC

GATCTTAAAA

CTACATCACT

TTACGTGTTC

729 INFORMATION FOR SEQ ID Wi SEQUENCE CHARACTERISTICS: LENGTH: 804 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/18323 99 (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .804 (xi) SEQUENCE DESCRIPTION: SEQ ID PCTIUS97/19575 ATGAACTACC CTAATCTACC TAACAGCGCT GAAATCACTA ACGAGCTTTT AAAGCAATTA AGCGAGCAAG TGGAATTAAG CCTTAAATGC TTGGATTTTT TTAAGAATGC GAATGAGATT CTGACTAACG CCGGCGAGAG CTTGAAATTA GAGTTTAATA CGAGCATGCA TGCCAACGAG GCCGAGAACA TTAAAAGCGA AATTAAAAAG AGACTTTTAA CGAGCTATCA AATCTTTTTA ATCACAAAAA ACAAAACCCA AAGCCTTGAA AATGAAATAA GCAACAATCA AACGCAAGCG GCTAATAATG AAATAAGCAA CAATCAAACG GAAAGCGCTA CAACGCAAAT AAACGCCAAT GAAAAAACCC AAGCCACAAG CGAGATCACC ATTGATTTTT TTGAGTTTGA ATAA

TTAGAGATAA

CAAAACGCTT

ATCGTTAGGA

GATAGCAGTT

AAAATGAAAG

CAGGAAGTAA

CTAGAAAATC

AACCAAGCCA

GCGATTACAC

ATAACTAATA

CAAGCGATAA

AAGCAAGAAG

GCGAACAGCC

TAAGGAGCAA

TTTTAGAAGT

TAAGAAATTC

AATACGAGCG

CCAATACCTT

AATTGATAGA

GAGATAACGC

AAGCTAAAAA

TCACCGAAGC

CTAACATTAA

CAATAAATAA

AGAAGTGAAA

CGCGCATTTT

GCTTTTGAGT

CATTGAGTGG

CTTTTTTAGC

AAACGCTAAC

AACCACGACA

TAACAACCAA

CAACGCTAAT

GAAAACGAAC

CGAAGCCAAA

CATCACGCAA

TTATCAAAAC GAAGCGAAAA AGACCGATCA INFORMATION FOR SEQ ID NO:16: SEQUENCE CHARACTERISTICS: LENGTH: 1632 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...1632 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: GTGATAGAGA CCATCCCCAA ACACTCTAAG ATTGTTTTAC CCGGGGAGGC GTTTGATAGT WO 98/18323 WO 9818323PCTIUS97/19575 100-

TTAAAAGAGG

ACTAGCACTT

AAAACAAATC

TACAATAATA

GAAGAATTCA

GATGCGATCT

CCTTCAAAAT

TATATACTCA

GTTGTTTTAA

TATGGCACAT

CTTAAGACTA

GGCTATGGGC

GTGGAAAAGG

TCGCTTTATG

CACAATTGTG

CTCATCAATC

AACCTAAACG

AAAACCTTTG

AGAAGCCCTA

ATAGGGTTGG

GTCCAGCAAT

TCCAATAAAA

ATCTTTGGGG

AGCGGCAATT

GTAGGGATTA

TATACGAACT

GGTGGGTGTT

CGTTTGATAA

CTATTTCTGA

TTATAATGAA

ATGGTAATAC

CCAATTTAAT

TAAACGCTCC

GCGTAAATCC

ACAAACAAGG

AAAATTCAGG

TAGGGGTAGA

TCAATTTAGA

ATAACGGGAA

ATAGTAATGG

GGGGATCCAA

CGGATGTCCC

AAAACGCCTT

CTAGTTTAAA

TAACTTCTAG

TTTTAGGGGT

CTTATTATGG

TGAGCTATGG

ATAGCCCTAC

GGTTAAGGGG

TAGATGTGGC

GCATCCCTTT

CTTTTGTTTT

TT

AATTGACCCC

TACTAACACG

ATATAGTAAT

AAAAAATGAT

GTTGAACATG

TTTTGAATTC

CGGAGTAAAT

TATTATTA.AT

GGTTGTAGGG

AGCCTATGCT

AGATTTAAGA

TATGACCTAT

CAAGCCAAAA

TCAGCCCGCT

GGCTGGCTTT

GCCGATCAAC

CACGCAAGAT

CGTTACCAAC

TAACGCTAAA

CATCATCAAA

TGGGGGGATA

AGGCATTCAA

CTTGTATAAC

TACCGGGTTG

AATCCAAAGA

CAATGAAGGG

TATACTTTCT

CAGAGGGTGT

GAAAATCCAA

TGTTGGCAAA

ATCGCTGTCT

ACTAACAGCT

GGGCGTGTTG

AATTTTAGAA

TTAGCCAATG

TTAGATCCTA

ACCATCTTGC

CAAAGAGTGC

GATTCTGATG

TTCCCTAGCA

TTAGGGGTAA

TACGCTAACT

TTAGCCAATT

CACCATTTTT

ATAGGCTATC

TACAATTACG

GATTTGTTAT

ACCAAAAGGA

AGCTATTATG

AACTACCGCT

AAAGCTAGCG

GCTAGCCACT

TTTTTCCAAA

TTGAAACGCT

ACAATTTCAA

ATTTCACCCC

TAGACTCCCA

CAACAGATTG

ATACTAAAGT

AAAAAATAGA

GATATGGCAA

AAAAACTCTT

ATGAATTCAG

CGGTAACGAA

GCCTCCCCTA

ACTACCCTAA

CAGCAGCGGT

TGGGGAGTCA

CCATGCTCAG

CAAACGCATC

AAAACTACTT

CTAAAGCTGT

TGGATTTCAT

ATTTTTCTTC

TGTTGAACAA

ATAAGCATTC

TCGTTTCTAG

TTAAGGTGTT

ATTTGAAGCC

CAATAACATT

CACTTGTCCT

ACAAACCGCA

ATCTTGGGGC

CGATAGCGAT

CGATCAACAA

AATTGATGCG

TGATGGTGAA

TGGCAACGAC

CCACACTAAA

AGATGGTCAA

TAATGTGTGT

TTCCATCTAT

TTGGCAGCAG

AACAAACTAC

CACCATCCAA

GCAA.AGTTTT

TAATGATTTC

TAATCAAAAA

CACCACTTAC

ATCTTTTGGT

AGTCAAAGGA

TAAATATTCT

CGGTGGCGAT

TTTCAATTAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1632 INFORMATION FOR SEQ ID NO:17: SEQUENCE CHARACTERISTICS: LENGTH: 1071 base pairs TYPE: nucleic acid STRAN'DEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NANE/KEY: misc feature LOCATION 1 .1071 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: TTGATGAAAA GCATTTTGCT CTTTATGATT TTTGTA.GTTT GTCAGTTAGA AGGCAAAAAA TTTTCACAAG ATAATTTTAA GGTGGATTAT AACTACTATT TGCGCAAACA GGATTTGCAC ATCATTAAAA CGCAAAACGA TTTGTCCAAT GCCTGGTATC TCCCTCCACA AAAAGCCCCC AAAGAACATT CTTGGGTGGA TTTTGCTAAA AAATATTTAA ACATGATGGA TTATCTAGGC WO 98/18323 WO 9818323PCT/US97/19575 101

ACTTATTTTT

ATCAACCCCT

AGGCATATTC

CAAATTTATA

ATCTATGTTT

ATTTGGATAG

TTTAATAAAG,

TATAACGGGC

CTGTGTTTCG

TATGTCCCTT

AAAATTGATT

CAATACTGGC

AACCCTTTTG

TACGATGTTT

TGCCTTTTTA

ACCAACGCAA

TTTGGACTAA

ATGACCCTCA

ATCCTATTAA

GTTGGCAGCA

AAGGTAATCC

AAAAAGATGT

TTTTGGTGTG

ATGATCAATC

ACAGGAGAGG

GTTATGATCG

TGGGGATTTA

TTTCCAATCG

TCATAGTTTC

TGAGTTTAAG

AGGCACGCTT

ATCCGCCCCC

TTTTAAACCT

CATTTCTAAT

TGAAAACCAG

GCGCtGGGGG

GGAAAAGGGA

CAACCCTCAA

GCGCCACCAT

CTGGCATGGA

TGCGCAGTGG

TATAGGGGTA

ACCCCCATTT

TTCCAAATCA

TATCTGGCTT

ATGCGAATGA

TTTGGGGGTA

GGTGTGGGGG

TTTCCAGGAC

GGGTG'TCKTT

GGCCTAAAAA

TTGATTGATT

TTTGAATTGC

GCTTTCCGCT

TTTA.ACGGCT

GGAATACGCT

TTCAATGGTA

GTTTTAGAGT

ATACCCAA-AC

TCAATTTCAT

AAATAGGGAA

GTGCGCAATG

AACCTGTAAT

CGGTGARCS C

TCATGGTCGC

ACATGGGGTA

AACTTTATGA

TAGGCTATAC

ATGGCGATGG

TGAACCCTTA

CCACCCTAAT

GCCTGTATTT

TAACTGGTTT

GCCTGAACTC

TTTTTCTGAA

TTACCAGCCT

CGTTAAAGAT

GGGCAACSCC

TTATTGGCCC

TGGTAACGCT

TATTTTCACG

CTACCGCATT

CTTGTATGAA

A

300 360 420 480 540 600 660 720 780 840 900 960 1020 1071 INFORMATION FOR SEQ ID NO:18: SEQUENCE CHARACTERISTICS: LENGTH: 2028 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .2028 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:

TTGTCTAAAG

GTGTGCGTGA

AGCGCTCTGC

TTGGAAAACA

AGAGAAATCA

GTGAGCATGT

ACGATCAAGT

AAAAATAAAG

GTTTATGGCG

GTTCTGATGA

GATTTATTTT

GACAAATCCA

ATTTTAGAAA

AATTTTTTAG

AATTGGATGA

CGTTTTGTGG

CTTTTAATGC

GTTTGAGTAT

GCATTTTAGG

ATTCAATGCA

CTTATACGAG

AAATCCAGTT

TTTTTAAAGA.

TGATGGAAAA

AAATTTCTAA

TGGATATTCT

TTTTCTTTTC

TAATTGGCGT

TCACCGAAAT

ATGGCTCTAA

CCGTTGAAAC

TCGCTTTGAT

TGGTTGCAGC

GAGCGATCGT

CGGTAATAAA

GGTGTCCTTA

AGATAGTTTG

CATGGGCATT

GTTAAAAAAC

CAGAGAGGAT

CCCGTCATTA

AAGCTTGCCT

TTTACCACTA

CATTGACAGC

TAAAGGTAAA

TTATAAAAGC

AGCGACTTTA

CTTTAAAATG

CATTGAAAAA

GAGTGCTATC

GAGCAATCGT

ATCATATTGT

AACAGCAGGG

CATTTCAAGG

GTCA.AAGAAA

TTCATTTTAG

TTGAGATTGA

GGGAGTAACC

TATTACAGGA

TTCAAGGAAA

TTCAGTAATG

GTGCTTTTGA.

GTGCCTAAAG

GAATACTTGG

CTAGGCAAAA

GACAAGGTCT

ATGGTGTTAG

TTGGAAGTCG

GCGTGGCGTT

TGAAAGAGAT

TTA-AGGAAGT

TGCTCCCTGA

CCAATTCGCA

CG CTTTTACG

CTTTAGCGCA

AAATGCCTAA

ACACGCAAGA

AAATCACTAA

GCGCGAATAA

CCACTAATGA

ATCCCTTTAG

CAGAAA.GTAA

ATGAGCAAGT

CCTTAATCAT

TTTCTAGCAC

GATTGTGATC

TTTAAALAGAA

GCAAAGTGTT

AGACACCAAA

TGTCGCTGGG

AGATAACGAT

AAAAGCGATG

CGGGGCGGAA

AGTGGTGGGG

AAACAGGAGC

AAGCTTGCAA

AGTGATGGCT

CCATAAGGAG

AGACAATCTT

GGGATCGGTG

AGCGATCACT

CTTGTCTCAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 WO 98/18323 WO 9818323PCTUS97/19575 102

TTCTTTAA.AT

TCTAATGACG

AAAACCATGC

AAAGCGGGGA

TTGAGAGACG

CCAAGCATTT

AACGCTTCGG

CTAGAAACTT

TGCGTGCAA.A

AAAACGATAG

ATTGAACAAG

ACGAATCTAT

GGCTTTGCGG

AGTGAGATTG

ATTAAAAACC

GTTACTGAGG

AAAGTCTCTA

TATTGAACAA.

AATTAGGGCG

AAGAAGACAG

ATTTTGCGGT

CGCTAAATGG

TCAAAATCTT

GTAGGGTGGA

CGTCTAATTT

ATTTAGAAAA

AAAATATCAC

GGAAAGACAT

TAGCCCTAAA

TGGTGGCTGA

AAGCCAATAT

AGGTTAAAGA

GCAATCTAAA

ACGATATTTT

TCAAGCCCAT

CATGCAAACA

GCAAGCCGTC

GCGCATCACG

GATCATGGAT

TGAAAGCTAT

ATTGGTTACT

TGCCAAAGAT

GGCTTCAAAC

CACTTCCATT

TAAAAGCATT

CGCTGCTATT

TGAGGTGAGG

TAATATTCTC

AGTAGAAGAG

AATCGCTAGC

AGAAGATGTG

TCTAGCGACA

GCGATCAATA

CAAGACACCA

GCTGAACCCG

TATTTGCAAG

TCTGGCTTGG

AACGCTTTAG

CTAGCGAACG

TCCCAACACA

CAAGGCGTGA

GTAGAAATCA

GA.AGCCGCAC

AAGCTCGCTG

GTTCAAAGCA

ATCAACGCTT

GATTCTTTAG

AATAAAAAGC

TTAAATTGGT

AAAATATCTT

TTAAAGTGGT

CAAGCCCTGA

AAAGCGTAGG

ATTTTAGAGG

GGCAAGAAAT

ATAGCGCGAA

AAAGCCTGAT

GCTCTCAAAG

TTAGAGATAT

GAGCCGGCGA

AAAGGACGCA

TTTCAGACAC

CTATTGAAGC

AAATCAGTCA

AGTTTTAA

TGAAGCGCGA

GCAAACCCAA

TTCAGACGTG

TTTGAAAGAA

GACTCACATG

GCGGATCCAA

CCAAAAAATG

TTTAAAAGAA

GGAAACTTCC

TGAAGCCATG

TGCCGATCAA

GCATGGCAGA

AAAATCCCTC

GAGCGAAAGC

CTTAAGATCG

AGAAATTGAC

1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2028 INFORMATION FOR SEQ ID NO:19: SEQUENCE CHARACTERISTICS: LENGTH: 816 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .816 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:

ATGAACATAT

TTAGACGCCA

GTGGGCGCTA

GAGAAAGGGA.

CTCAATGACG

AATTTGGACA

TTTTATTCTC

CCAAATGATC

GCTCTCAAAG

AACATCAAAA

GGGGCTATCA

GAAGATAAGG

GAAGCGATAA

GATACCTATA

TCAAGCGTAT

AACACCACA.A

ACCCTGTGCC

TCAAATTAGT

GCTCTTTAGA

GAAAAATGCA

AAAAAATCAC

CGGCCAATCA

ACCCAAGCAA

TCAAACCCCT

TAACAGGGAA

ACT CGCCTTA

AAGCGTTGAT

AGGGGGCGAT

TATTTGCGTA

AGAAAAAAAA

GCATGCGCAA

GATCGTGTCT

CGCGAATTAC

CCTTGTTGGT

AGACATTAAA

AGGCAGGGCG

TCTATACGCT

AG.AAGCTGCG

TTATGCCTTG

TGCTAATCTT

TGAAGCCTTA

TATCCCGGCT

ACCGCTATTG

GAAGACCACA

ATCTTGCAAT

TTTACGGATT

TTCCAGCACC

TTGGCCAATA

AACCTTAAA

TTGATTTTAC

ACGGAGTTTG

TTATTGCCTA

CAAGCAAAAC

GTAGCCTCTC

CAGAGCGAAA

TTTTAA

TTTTAGGTTT

AAATCACTCG

CAGTTGTGGA.

ATGTGTTGCC

GCCCTTATTT

TCCATGTGGA

AAGGCTCAGT

TCCATAAACA

ATATTGTCAA

AGGTTTTAGG

TCACCGGAGC

GTGAGGATAA

AGACCAGGAA.

TTTTAACCTT

TGAGCTTAAA

TGATTTGAAA

TAATTTAGCG

GGATCGGTTT

GCCTTTAAGA

GATTGCTGTG

AGGCCTTATC

AAATCCTTAC

GGATGTGGAT

CTTATTTTCA

TGCGCAAGAT

ATTCATTTTG

WO 98/18323 PCT/US97/19575 -103 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 486 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...486 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGTTTTTTA

GGCTGTGGGA

ACGTTTCAAA

GGTAATTGTG

CAAGTTACTC

GATCAAAAGA

GTGATGATGG

TGCAATATTA

AAATAA

AAACTTATCA

ATGGTGGTGG

TCGACTCCAA

CTGTCAATTT

CAATCTCTAT

AAGGGTTGGC

AACCTCAAAC

TAGAGGCAGA

AAAATTACTG

CGGTGAATCG

AGCAGATAGC

TGTTCCAGTA

ACAGGATTTT

AAACATAGCA

CCTTAATTTT

AATACAAACC

GGCGCGAGCT

CCGGTTGAGA

ATTACTATTC

AGTGAGACGT

AAAGATATGG

AATAAAATTT

GGAGAAAGTT

GACAAAGGCG

GTTTGGCGCT

TGATTGCAAA

AAGGCGTGAA

TTCAAATGGG

CAAGCACTTA

CTCAATTAGA

TAAAAGGCAT

CTTGGACTTT

GTATTTAGTG

TAGCGAGGGT

GCTTAATAGA

TGTTTTAAGT

TAAGATATTT

GCAAAAGGGT

TTCTCAAGGG

TAACTTTGAT

120 180 240 300 360 420 480 486 INFORMATION FOR SEQ ID NO:21: SEQUENCE CHARACTERISTICS: LENGTH: 1014 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...1014 WO 98/18323 PTU9/97 PCT[US97/19575 104- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2l:

ATGATTAGAT

CTAGGTGCTA

CGAGTAAAAC

GGCTCTCAAT

GAAAAGATTT

AAAGAAGACA

GCTAAAGTTT

CCAAATAAAA

TTTATTGATG

CTTGGCATTA

ATTAGACAAT

GCTATGGCTA

CAGCTCCATA

ATAGAGCTAA

TCTAAkATATC

TGGAGAAATA

GCTGAAkATAG

TAAAAGGTTT

CTGCTCCCTT

TACACAATAT

ACTTGAATAG

TTGAATGCGT

CTGAAGATAA

TAAGGCAAAA

AGCAACTTCA

ATTGGCACGA

AAGAATATAG

ATAAAAAAGA

ATATGAGTGG

GTTCAAATAA

CCAATATCAA

CCATTCATAA

AGATTTGGGA

GAATAGTTTG

GAATAAAACT

AATGGCAAAG

CAAAGAAGAT

TGGTTGGAAT

AGAAGAAGAA

AGAAGAACTt

ATTTATGGCT

AACCATGCTT

ACGCTTTGGG

TGATGAAGGA

TTTTGAAGAA

CGAAAACGAT

TATTAAACCC

AAAAGAATAT

AGATTGGGGA

ATGTATTAAG

GAAAAAAAAT

TTAAAAACAA

CCTTTATTAA

ACGCTGACTA

TTATCTAAAG

AAACATAAAC

GCAAAAAAAA

TTTGAAATGA

GAGAACGCTT

GGTATAAGTA

AAGATATTAG

AGCACTTATG

TATAAAATTA

TTAATGTCAA

GTTATGGGCT

TTTTTTGGTA

AATAAAGTAA

ACTTATTCTA

GCTTATTAGC

GCGATGAAGA

GCTGTAATGC

AATTTCCGCA.

AAGCCCTTAA

tCAA-AGAAAT

AAGAACACTC

TTGATAATGG

GAGAGAATAC

CCTTTGGCGA.

ATACTAGACA

CTTGGTTAAA

ACACAGAGTT

GTAATATGGA

AGGCAAAAGT

AGTCCTATGA.

TCTCTCATCA

TGGGGTTTTA

CTTATTGAAA

TAAGGTGGAC

AGAATATAGA

TTTAATCAAT

TAAAGAAAAA

TAAAGAATTC

AGCTGAAAGT

TTATAAAGCA

AAGAAGTTAT

AACCTTATCT

ACCCAAATAT

GTTAAATATG

AATAGATGGT

CCCAGAAACT

CAACACTACC

CTAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1014 INFORMATION FOR SEQ ID NO:22: SEQUENCE CHARACTERISTICS: LENGTH: 1251 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1251 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: ATGAAAAAAT TAGTTTTTAG ACTCCTTTGA TTGTCAATGA ATGGTAGATA GTATCAAAAG CAGTTACAAA AAGTCAATAA ATCACTTTAG CCAATCCTAT

AGATACAACT.ATGAGAATTT

AGAAACAAAT ACTTACAGCA AAGATTGTCA ATCTTAAAGA ACCGCAAGAG ATGTGCAAA.A CAATCACTTG CTGGGGAATT AACGATAGTA ATTATGAAAG CAAAAACGAA GATTTTTGCT

CATGCTTTTA

CCCAGAAACC

ATACGAAGAG

CATGATAAAT

GCAAGTTTTA

AAAGCAAAGC

ACAATGCCCT

TCTCAATAAC

TCTCATTCAG

GAGTGGTAGA

CGAGCAAGCT

TAGAGTAAAG

TGTTGTA.AA

CATGTAAGTC

ATTATTTCTA

ACGACTAATT

CAAAACGCTC

ATAGAAA.ATT

TGGCTTA.ATG

CTAATCACCA

TCCATTAGTG

GCGTGGGGGG

CTTTTAGCAA

AAAAAGGTTA

GCGTGTTTGC

AAGCCACTAT

AGGCTCAAGC

CTTTGATTAG

AGTATCAAAT

GGAACGCACA

TCAATGCTCT

AAAATGGCGA

GCAGTGGCTA

AAATGTTGTG

CAGGCAATAA

ATGATAATAA

AGAGGGGGAA

CATAGGCAAA

TCAAGTCAAT

TAGTAGTGCT

AGAGAGCATT

AAATTTGTTA

TACTAACAAT

ACAAACCCAA

TGGAAACATG

TAAAATGGTA

CCCAGAAGAG

GCAGTTAAAA

WO 98/18323 W098/8323PCTIUS97/19575 105-

GATAAACTTG

GACCCTACAG

GGTAA.ATGCG

CAAGAAATCC

CAAGCCTACG

ATTACCAATC

GATGATTATT

CAATTAACGC

AATGTTAAAT

ACCCATTTCT

CTAACCATAA

ACCCTATTAA

AAACGCTCAC

CAAATTTCAA

AAATGCTCTT

TTAGGCAAAA.

AAAAAAGAAT

TTGACCAATT

AAAAAGACTT

TAAGCAAGGG

AAATGTATTT

ACTTGATTTA

TCAAAGGATT

TTTAAATCAA

TAATGATGGC

AAACGAAAGA

TGGCTTTCCC

GATGTCCTAC

ATACATTATT

AGGACAACTC

ATCAAAGCCT

AAATTACTTA

ACAATGGCAA

TTTGGGGAAA

GAAAGAGCTA

ATTTTTAGTA

AAACTGAGTT

GCACAGAAAA

GCTTAGATAA

CCAATAAAGA

CTCTAAAATA

TGCAAAGCGA

AAGAAAACCA

GAATATACTT

TATGGGATTA

TGGTGTAACT

TAAAGAGACA

CGAATTAGAA

CGCTCAAAGC

TTTAAAAGAA

GATTATGACA

TATAGACAAA.

TCAAAACCCT

A

780 840 900 960 1020 1080 1140 1200 1251 INFORMATION FOR SEQ ID NO:23: SEQUENCE CHARACTERISTICS: LENGTH: 1131 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1131 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:

GTGAATAAGT

TTTTCTTTAA

AATGACGATG

ACTAACACGG

GCTTTAAAAG

CCTCCCATGG

TTACTGGCCT

ATTTTCCCTG

ATCGCCACTA

TTTTTGATTA

GATATTTTTG

TATTACAGCA

ATCACTCCCC

TATAACGGCT

CTGCTTTCTA

GGCAATAAAG

CAAAGCGGCA

GCCCCCATTG

TTCTTCCCTA

GGATTAAAGG

TCTACCACCA

AGGTGAAATA

AAAGCTCCAA

CCCTAAACTC

ATCCAAAAAC

CTCGCATCAC

TGGATAACCC

ATGAAAACAA

CGCCCATTTC

CAAGCATGGG

ACAATAACAA

ATGGCATTAA

TAGTGGGGGA

CGCTCACTAA

AAGAGGTGAC

TGGGGATCAA

TGGTGATTAG

TACCCAGAGA

GGCGGTTGTT

AAAGCCAAAA

CCCCTTACAA

AGACGCTACC

CAAAGAAATG

AACCCCCCCT

CCCTTTCAAG

TAATGGCATT

GCTTTTACGC

TAGCCAGATC

CAAAGCCGTC

AATGGGCGAA

TATCATGCTC

ATTGATTGAA

CGGCCTATTG

TAATTTCTTT

TCAAGTGGTC

AGAGGGGAGT

GAATGAAGTC

TTTGTAGGGG

GCCCCCCTAA

GACTACACTT

ATCAAAGCCT

AATTATTCCA

AAAAAAGACT

CAAAGCCCTA

GATAGTTTCA

ACCATTACAG

GCTGGTA.AAG

TTAATCCCCA

TACCGCTTGG

ACTAACGCTA

AGGAATTTCC

ATTGGGATCA

GGGGATTATC

AATCAAATTT

AGGGTCTTCA

ATCGCTGAGT

GTTTTGCAAC

ATAACCAGCC

TCACTCAAAA

TACAAGAACA

AAGAAGAGAC

TTTCTCCAA.A

AAAATTACGA

CTAACCTTAA

CTGACAAAAT

TGATTGCGCA

AAGGCTCTAA

ATATTGTATG

AAGGGGCGGA

AACGCTATGG

CTTCGGCTTT

TTTTATTGCA

TAAGAGACAA

TTTCGCCCAA.

TTTTGAAGTG

GATTACAACC

TAGCCTTTTG

CCCACAGCCA

GCTCAAAGCC

TTTTACTAGC

ACAATTAGAT

AGAAAACCTG

AGAAAAAGAC

GATACCCGCT

AGTGGAGAGC

AGTCATAGGC

GAGTCGAATC

CATTAAAGGC

CGTGCCGTTA

AAACAACAGA

ATTGATGAGG

GAGCAAGATC

TACTGACATC

A

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1131 INFORMATION FOR SEQ ID NO:24: WO 98/18323 WO 9818323PCTIUS97/19575 106 SEQUENCE CHARACTERISTICS: LENGTH: 2751 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NA1M.E/KEY: misc feature (B)_,LOCATION .2751 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:

GTGGATTTGA

CTAATCAGCT

GTTTCTATTC

ATAAATCTTA

TTAAAATTGA

AAATTAATCA

AGAGAAATTA

ATAGGGAAAG

GCAAGTGAAA

AAAA.TTTTTA

ATTAAAGAAA

TTTGAATCAA

TCGCTGATCC

GAGTATAAGA

AGTCATGCCG

AAACAGATAG

GAACCAATAC

TATTTGTTCC

TTCAAACAAA

ACAGCGTTTA

GTGCCAATCA

TCAACCAAAG

TTATTTAATA

AGATCAAAAA

AATATCTCTA

TCAAAAGATT

CAACTTGAAT

ATTTTAGAAT

CTTTTAGCGA.

CATAACAATA

GATTGCAGAA

TTCCAATGGG

TTTAACCATA

AGAAAGGAGT

GGATCCAATC

ATCCTTTTGA

CCATTAACAA

TAGCTTCTTA

GCGAGCTTGT

AACATTTAAG

TAAAATACAA

GCAAACAAAA

TTAAACCACA

AAACTACCGA

TAGACGAAAA

ATATTGAAAA

GAGAAATTGA

TTAATGATCT

TTAATGATGT

ATTTATTAGT

AAAGATCTTT

CTAAAAATAT

GCAAAAATGT

ACTTTCATCT

TGAAAGAATA

AGACTGGTCT

AAACAAACTT

TAAAGTTTGA

AAAAATACTT

TTTTTTCAAT

TTTTTGAGAA

ACAACATGCA

TCGTTCAAGA

AGCTTCCTAG

AATCCCACGA

CGTTTAATTT

ATATTATCTA

TTAGGAAATT

TAAAGAAGTC

AAAACATGTA

TGACGACTAT

CAATTTATTA

AACTGAATAT

CGGCAACAAT

CGCCCCTAAT

ACAATTAGCA

AGATATGGAA

CTTTACAAAA

ATACCCTATC

ACATGATGAA

AAATCACTGC

GCTCAAAAAT

GTCTAAAGAT

CAATTCAGAA

ATGGGAGAGT

TGGTGAAATC

TTCTGAGTTC

AAATATAAAT

CAAAGAGCCA

TGCTAGCCAA

TAATCCTAAT

TAAAGATTTA

GCAAGAAATA

TCAAAAAATA

TGATACAAGT

ATTAAAAATA

TAGTCCCCAA

AGAGAAATAT

TCACAATGAG

CATGTTTGGC

TGTCATGGAC

TTTAAAAGAA

AGTCATAATT

GAAGCTTTAG

TCAAATATTT

GAATCATTTT

GCCAACGTAA

CAATTGGTTA

AAAGAATACA

AAAATTTATT

GACATCTTAA

TTCACACCAA

AATGAAAATT

ATAAAAAAGG

AAAAATGAAT

ATCCAACAAA

ATTAAATCCA

ATTGTGCGAT

ATAAAAATTT

AAGGATAAAT

GCAGAATATT

AATGGTTTAT

AAAATCACAG

TTATCTGGGC

AAAATTTGGA

GAAATCTATT

GATCAAGAAT

GAGAGTAAGC

TTTCTTTTTG

GATTCTTTAA

GATAGTTACC

ACGGAACATG

CCAATCATCT

TTTCTTTATA

GAGCCAGCCA

TACGCTCATA

TAAAGGAATT

GGGAACAATG

GCACTTTTGT

TAGATTTTTA

CCAATAATCT

AAAATTTTTA

AACCCAATCA

CTCATTTAAA

AAAAGCTAGA

AAACTGAAAT

TTAAACGGCA

ATTTTGAGCG

GCAATAGCGA

TATGCAAAAA

TGATGTGTCA

ACAGATACAG

TAGATAATGA

TTGAAGCAAA

GCCGAGAGTG

CTCATCAATT

ATAATGACCT

ACTGGTTTTT

TTCCTTTAGA

TTGATAGTCA

CACTAAAAAA

ATGATAATAA

CTAAAGGAAG

TTACAAAAGA

AATTAAAAAT

AAATAAAACT

TAAGCCAGCA

ATGTGGGATC

CTCATTTGAG

AAAATCATGT

ATCAAAAACG

CAGTAACTTC

GAGTGATTTT

TAAAGATAAA

GCTTTTCAAA.

TCAGTGTATA

ATTTTTTATA

AGAACTTAGT

GGAATTAGAT

TAAGGATATT

ATTTAATGAG

AAACAAAGAG,

AGAAGAGCCG

TTATATAGAA

GTTTTATTTG

CAATCTTTTT

AAGTGGCATT

CAAGGAAAAA

TAACCCCTAT

TGAAAAATTC

TGAAGCCATA

TCAGCTTTCG

GTTCAATAAA

TGAATCGTTC

GATCAAACAA

CGATATACTG

TTTTGCAGAA

ATTTAATAAG

TCGTGTCCGA

TGAAGTTTAT

AAGCACCGGC

ACATTTTAGT

CGTGCCAGCC

TACTTTTGTT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 WO 98/18323 WO 9818323PCTIUS97/19575 107-

TTAGCCACCC

GAAAAGGAAA

AGCAAAGACT

TTTCATAACC

TTGAGCGCTT

ACTTTCTTAC

AAACTTTGCG

TTTAACCAAC

ATCACCATCC

AGCGCAAACG

AAAACAAGGC

TTAAAATTAT

ATGACCCCTT

CAGAAGGCTC

CCGACGCTTT

CCCAAAAACA

TTAAATTGTA

CCATTTCAGG

AGTTAGACAA

AAGCAACGAG

TACAACTCTC

ATAGAAACAA

TTTTGTATGG

TCAAATGGAT

TTTAGTGGAT

TGTAATTAAG

GGACAAAATC

CCGAATCATT

TTTGCGTTAC

GCTTAAAAAC

TCACCCTATT

CGAACGATTT

AGACTGCGAT

ATACGCTAAA

CGGAGAAGAT

TGCATGGGCT

ACGGATCATT

AATCACTTTA

AAACGCTCTT

TTTGTAGAAG

AAAGAATACA

GATTCAAACG

GTTTTGACAG

AAAAGAGCTA

AGGCATTTCA

AATAAGCAAA

GCGATAGAAA

ACAAACTTGA

TAGATGAAAT

ACTATCCCCT

TAGGAGTGGG

GCATCACGGA

AGGACALACCC

ATATGAAAGA

ACGATGACAG

ATGAAGAAAT

AACAAATTGA

TGGAATTGAG

AACAAACAAA

TCAAAAACTA

AAGGATTGTG

AAATAATGCA

CCAGCATGTT

TTATTGTTAT

CATTCCTTTC

AACCATTGAA

AAAATGCGTT

GCATGATCCC

AGATTGTTTC

CATGGCTTTT

AAGAAATTTT

A

2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2751 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 531 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAMVE/KEY: misc feature LOCATION 1. 531 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGACTGCAA TGATGCGTTA TTTTCACATC TATGCGACCA CTTTTTTCTT CCCTTTGGCG

CTTCTTTTTG

AAGATCAAAG

AAAGGCTTTA

AGGGGAGCGT

CAAACGAAAA

GCTAAGGTGG

TTTTACTTGA

GTTTTAATAG

CGGTTAGTGG

AATGGGTTTT

TAAAAGAAAA

TAGTCATTGG

TCAAGACCAT

GCATCGTGTT

GCGCGTTTTT

GGAGCGTGGT

GCTTTCATTG

AGAAAAATCC

CCATATCGCT

CACGCCTTTG

TGAAAGGGGC

TCAGGCGCTT

AATGGTGGCT

GTTCTTTGGA

CTCTTTAAAG

TTAA.AAAAAG

ATGCCTAAAA

TATGAAATCA

TTTTTAGGCG

TTAGGGATTT

TTTAAAGACA

GCGATCTATT

CGCGCCAAGA

AAGAACGATT

AGATAGAGCC

ACCTTGAAAC

CGCTCATCAT

TTTGCGTGTT

CTAAACGCAT

GGTCTTTGTA

CACTGGCGCT

GGACTTTTTA

TAGAGAGTAT

TAAAGGCACT

GCTGCATAAG

TTTATTGTTG

GTTTATAAGC

G

120 180 240 300 360 420 480 531 INFORMATION FOR SEQ ID NO:26: SEQUENCE CHARACTERISTICS: LENGTH: 669 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCT/US97/19575 -108- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .669 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:

ATGTTTAAAA

ATTATTGGCA

TCAGACTATA

CAACGCAAGC

AACGACCTTT

AAAAATCTTT

ATTGACTTAG

TTAGAGCAAA

CTTACAAGTA

CTCCTTAAGA

GCTAAAACTT

ACGCTTTAAA

CAAATGGTGC

ATTTTAAAGC

AATTGGGAGT

TTAAATTCTA

TAAATAAAAC

CTCTTAGCCA

ACGCTCTTAT

TCATCGCCAC

ATGGCAACAT

TTAACTTTAA

TATACAAGAT

TGGAAAATCA

ACAAAACAAT

TGTCTCTAAC

TCAATTTTTT

CTACGAACAC

TCACCCACAA

AAGACTATCA

TCATGATCCT

TGCTCAATAC

AGAAAAACCA

TTTTCATTTA

ACGCTTATCA

AATATTCCAT

CTATTCAACT

CACAAAAACT

CTAAGCGACG

TTAGTTATTA

AATCTCATAA

ATTGTCTTAG

AAACCTTTAA

ACCACAAAAG

AAAATCATAC

ACACTATTCT

ACCACGACAA

ACCCACCTGG

GCACTCTAGA

GACAAAAACA

TGGATGAACC

GCTTGCGCAA

ATAGTTGCGA

ATTCTATATT

ACTTATTAGC

TAGTACAGCC

AGGCATTAGA

TGTTATACCA

ATTAAACGCA

TTTGTTTGAA

GCGCTTAAAA

AGAAACCAGT

CACCCAACAA

ATGGGTATTG

AAAATCTGTA

GTTACTAAAG

120 180 240 300 360 420 480 540 600 660 669

GATATTTAA

INFORMATION FOR SEQ ID NO:27: SEQUENCE CHARACTERISTICS: LENGTH: 1221 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 1221 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: ATGTATGCGG CTCATCCTAT TAAACCCATA AAAGCCCCTA AACTCAAATC TCAATTTTTA AGGCGTGTGT TTGTGGGCGC GTCCATTAGG CGCTGGAATG ACCAAGCATG CCCTTTGGAA TTTGTGGAAT TAGACAAGCA AGCCCATAAA GCGATGATTG CGTATCTGCT CGCTAAAGAT TTAAAAGATA GGGGTAAAGA TTTAGATTTA GATCTTTTAA TCAAATATTT TTGCTTTGAG TTTTTGGAGC GCTTGGTTTT AACCGATATT AAACCCCCTA TTTTTTACGC CCTCCAACAA 120 180 240 300 WO 98/18323 WO 9818323PCT/US97/19575 109-

ACGCATAGTA

TATTTTTCTT

CAAATTTTAG

TTTAACCCCA

AATAACGATC

AGCATGTTTG

ACCAGTGTTC

TTGAAAGCTT

CCCGAAATTT

CATTGCATTA

TTGGGCGTTC

GACAAGTCTC

AGCGATGAAT

TTTTTAGAAG

GCTAAAAACC

TTGTTTAGAG

AAGAGTTAGC

TAGAGGAACT

AGAGCGCGCA

ACATGTATGG

ATTTGTTTGA

GGCAGTTGCG

TAGGGCATAC

GTAAAAGCAT

TAACCCGAGA

AAGAGATTGA

AAGAAGATTT

ATCAAATCGT

ATCTTGGGGT

CCCAAATCTC

TTTTAGAATT

ATTTTAAGTA

TTCCTATGTT

CAAAGAGTAT

TTTTTATGCG

CGTGAAAGAG

AGGGCTTTTT

TTTCCAAAAG

TTTATGCGTG

GCGGATCAAT

CATTATCACG

AAAAAAGGAA

GAAATATTTC

TTTCACTAAA

TTGCGGGGAG

TCTTTCTCAT

GCGATCCCAA

GCGCAAAGTT

TTAAGCCACA

TCTAAGTGGG

ATTAAAGATA

G GGG ALA-AAA G

CGCTGGAGCC

GCGATTATGG

CATTTtTTGG

CCCATCAAAC

ATGCAAAACA

ACCGAA-AACG

GACGCTGAAG

CTTTTGAAGG

GGCATTTCTA

ACGGAACTGC

TGCAAGATGA

GGCCTCAAAT

AGTTTGATAT

AAATTGACAA

AAGATTTGAA

AAACCCCAAG

GGTATTTATT

GCGGGCTTTT

AAAGCGTTGC

AAGTCTATTC

AGTTTAAAAA

AATTATTCAC

TGTGCGATCA

GCTACGATTT

TTGATTTGGA

AATCAGTGCG

TTTAGAAACT

TATCTATCAT

GCAACTCCAC

AAAATTGGTG

AGTGCCACAA

GAGTTTTGAC

CCATGATTTA

AGGGCTTGAT

CTTTGTGTCT

CCGCTACAAA

GCTTTATAAT

TTTGAGCGCG

AATCCAAGGA

TTTAGGGAAA

360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1221 INFORMATION FOR SEQ ID NO:28: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 1008 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc-feature LOCATION .1008 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:

GTGTTGTGGG

TCTAAAAAAT

AGAACCCCAC

GAACCTTTTG

TTGAGCGGTT

CAAGCTGTAG

CCCCTTTTTA

ATCAGTAACG

ATCGCGCTTT

ATGGTGCTTG

GGGGCGTATT

AAAATCAGCG

AGTATCCTTA

CACACCCTTT

GCGTTTATCC

TGCTATATTT

CCATGCTCTT

GAGCCGGGGG

AGATGCCTTT

TTTTAGAAGA

GGGTCGTTTG

GCTTGCCTTA

CTATTAATAT

TAGTCATTCA

GGTTTATGGT

TTTTGGGTTT

TGTTTTTTGG

GGCGCAAAAT

TATTTAAATT

TTATTCTATG

TTTAACCAGT

TGTGGATAAC

GCTTGGGATC

TAAGGGGCCT

CATTAACCTT

CATCATTTCA

TTTCATCGCT

CATTGACGGG

TTATATAGAC

GTTAAATTTC

GGTGTGCGGG

GCTCAATTTA

AAAACGCCAG

CTTGCAACAA

CAACCTGCCT

TTATTTATTT

GCTAATAAAA

TTTCTTTCTT

TTTGTTTTCT

TCATTAAGCC

TCAACGCCTT

TTTTTATTCG

TTTAACGGGC

CCTAGCAGTT

CCTTCAGGAA

ATTTCTCTCT

ATGCTTTATC

AAAGCCACCA

CGCTCTTTCA

TTTATTTTAM

GCTCTTTGAT

TCCAAGGCTT

TTGCGTTGGC

TAGGGCTATC

CCAAAATACG

TAGTGGTGAG

CTATTTTTAT

TTGCATCTGG

TGTCTTGTTT

AGATTTTTTT

TGCATTTGAG

CGGTCATAGA

TGCCGGATAA

ATTAC CCTAA

TAAGCGTTTT

TGTTTTGTGG

CCATCATGCA

TTGTTATCTT

GCTAGTGTTT

CCTTATTTTG

CGATTTTTCG

GCTGGTGGGT

GATTTGCGCG

GCTCGCTTAC

AGGCGATGGG

TTTGGAGCAA

GGTGCTTTTT

TTTGCATTTG

CCCTTTATGC

GTTTCGCTTG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 WO 98/18323 PCTIUS97/19575 -110- GACGCTTATG CGCTCATTGT GATTAGCCTA GTCTTTATCG CATGCTATTT AATAGGCTAT 960 GCTTATTTGA ATAGGCAAGT TTGCGCTTTA GAAAAGCGGG CGTTTTAA 1008 INFORMATION FOR SEQ ID NO:29: SEQUENCE CHARACTERISTICS: LENGTH: 291 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...291 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: ATGAAAAAGG TTATTGTGGC TTTAGGCGTT TTGGCGTTCG GATGTTAAGG CTCTTGTAAA AGGTTGTGCC GCTTGCCATG GCTTTAGGTA AAAGCAAAAT CGTTAACATG ATGAGCGAAA ATGGCTTTTA AAAGCGGTGC CAACAAGAAT CCTGTCATGA AGCGATGAAG ACATCAAAGC TTTAGCCAAA TACATCCCCA INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 471 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...471

CAAATGTTTT

GGGTTAAGTT

AAGAGATTGA

CCGCGCAAGC

CTCTCAAATA

AATGGCAACC

TGAAAAGAAA

AGAGGATCTT

TAAAAAATTA

A

120 180 240 291 (xi) SEQUENCE DESCRIPTION: SEQ ID WO 98/18323 WO 9818323PCTIUS97/19575 -11II

ATGCGAGATT

GAAAAACTGG

GGGAAAAGCG

TCAAACATTG

AGAGAAGATG

TTTTTAAACC

AAACGCTTAT

TTATTAGATG

TCAATAACAT

ATCTGGAGTT

TCCTTATTGC

AAGTGGAATT

AGCATGAACC

AAACAAGCCT

CTAACGACAG

GCTATATCCA

TCAAATCACA

TAAAGATGGC

GAGCCTTTTA

GATCGCGCCT

CTTAGtTATT

ATCTAAAAAC

ATTCAGCCAG

AAATAAAAAT

CGCTTAAAAG

TTGAGCGCGA

GGGGCGTTTG

TTTTTAGACA

AGCGTGATTA

ACGCTCAAAG

AATGAACTCA

AGGCdTTTAG

TGCGTCAAAA

TTAGTGGGGC

GGCTTAAAGA

CGGAAGAATA

AAAAAGAAAA

CGTTATTAAA

ACGATATTTT

CCCCCTTTTA

TGCCGTTTTT

TAGTGGGGTG

GAGCAACGCT

CGGCATTTTT

AACACGCTAT

GGGGCTTATT

AATGCTCTCC

G

120 180 240 300 360 420 471 INFORMATION FOR SEQ ID NO:31: SEQUENCE CHARACTERISTICS: LENGTH: 357 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAI'E/KEY: misc feature LOCATION 1. .357 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:

GTGATGCTAA

ATGAGTTTAT

TTAAATGATT

AGCAGAAAGG

AA1AGAACAAG

AAAAAATTTG

TGGCAATTTT

TCGCCAATAT

TTGTTTTTGG

CTATGGAAAA

TAGATATTAG

ATTTTGTTAT

TACCCCTTAT

GGGGTTGGAG

TATAGAAGTG

TCATCTTATC

AGAATTTGAG

TTTTAGCAAA

ATTCTTATTT

CAAATTTTTT

GGGCTTGATA

GGTCTTTTTG

GATTTACGCC

GAGAAAACTT

TGAAAATGAT

GCAACAGAGA

GCAATGCGAG

TCCAAGCTCA

AGGCTTTTGG

ATTTTCATAG

GAAAAAGTCT

CATTAAAGAT

AAAAAATCGT

ATTAAATTTT

AAATGATACT

AAGCTAA

INFORMATION FOR SEQ ID NO:32: SEQUENCE CHARACTERISTICS: LENGTH: 1068 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM.: Helicobacter pylori WO 98/18323 WO 9818323PCTIUS97/19575 112- (ix) FEATURE: NAME/KEY: misc feature LOCATION .1068 (xi) SEQUENCE DESCRIPTION: SEQ ID NQ:32:

ATGAATATCA

CATTTATGGG

GGGAATTATT

GGCTGCACGC

AAAGCCCTAG

TTAGGGGGGC

GCTTACGCTA

TATGATAGAA

AATTTTGATA

GAAGTCAAAC

GAGGGGCAGG

GAAGATTTTG

GGTTGCGCGA

AAGGCTTTTA

ATGGGCTTTA

AATTATGAAA

TATTACAACA

GGCATGAAAC

AAATTTTAAA

GGAAACAAGA

CTAAAGCGGC

AATTAGGAAT

AATATTATAA

TTTATGATGA

AGGCATGCGT

AAATCAAAGG

TGGCTAAGGG

AGAGCAACCA

CTTGCCGAGC

AAGTGGCGTT

GTTTAGGCTC

ACTATTTCAA

TGTATTCGCA

GAGGTTGCGA

TGAAAGATAA

AGGCATGCGA

AATATTAGTT

CAATAGCTTT

GTCTTATTTT

CATTTATGAA

AACCGCATGC

GGGTTTAGGC

TTTAAAACAC

CAATGCCGCT

GTGTTATATT

TAAAGCCGTT

GTTAGGGAGT

TGATTATTTG

TATGTATATG

GCAAGCATGC

AGGGGACACT

TATGGGCGAT

AGAAAACGCC

AAATCTCACC

GGAGGOTTAT

TTAGGGATTG

AAAAAAG CAT

AACGGGCAAG

CAGGCTGATG

ACGGCTCAAA

CCTGAGAGTT

CAAGCGGTTA

TTAGGCACTG

ATCTATTATT

TTGTTTGAAA

CAAAAAGCTT

TTGGGCAGGT

GATATGGGGA

GTTTCAAAAG

GAAGTGGGTT

ATAATGATTT

AAACTCAGGG

TTTTTTTGAG

GTGAAAGAGC

GCAACGATGG

GCACTAGAAT

ATAGGGAAGG

ATTATCAAGA

G CTACAATTT

CTTACTATCA

CCTATGAAAA

TGAAAGCGTG

ATGGCGATGC

GCGCTTTAAA

ATGTTAAAAA

GCGCGGTGAG

ACTTGAGGAA

GCTTCGCTCT

ATGACAAGGG

GGTATTAG

CTTGAACGCC

CTATAAAAGC

GGTGAGTGAA

AGATTATAAA

GTGTTTTGGC

AGCCATTGAC

AGGCATCATT

AAAAAGCTGT

AGGCTTTTTA

CCGATTGAAT

AGGGCTTGAT

CAATTCTGGT

AGACCCCCAA

TTGCTCTAGG

AGCCCTTGAT

AGCGGGCATG

CTGTAAATTG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1068 INFORMATION FOR SEQ ID NO:33: SEQUENCE CHARACTERISTICS: LENGTH: 582 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .58*2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:

ATGAAAGAAA

ATCGTGGTGT

TTCAAGGGTC

TTTAAATCCA

CCCATTTTGC

TTAAACAACG

AAAACTTTTG

TTTTAGTGGT

ATAACGAAGT

ATTATCGTTT

CCTATTTTTC

CTTTGATTTT

GCCTTTAGGA

GTTTGCCCTA.

GGATTTAAAC

TTCAGTGGGT

TAAAGGCACG

AGAAAAGTCC

ATCATGAGCG

AAAAATTCGC

TTTAAC!GCCA

TTAAAGCCTC

CATGGGGATA

AACACGCTTT

TGCTTATTTT

CTAAAAATGA

TGCTTAAAAC

TTACCGAAAG

AAAAAATCCA

ATGCACAATT

TGGGCTTGGG

TTTAGTGTAT

TTATGAAAAC

C CC TAAAAC C

AGAAAACCTT

GCAACCGCTC

120 180 240 300 360 WO 98/18323 PCTUS97/19575 -113- AAACCCGCTT TAGATTCGCC AAATATTCAA GTGTATTTAG CGTTCTATCC CAGCCAATCC CAGCCCAGAT TATTAGGAAC GCTTGATTGT AAAAACGCAT GCGAACCTTT AAAATTTGAT TTGTTAGAGG GCGATAAAGT GGGGCGCTAT AAGATCCTTT TTAAATTTGT TTTTAAAAAT AAAGAAGAAT TGATTTTGGA GCAACTGGCT TTTTTTAAGT AG 420 480 540 582 INFORMATION FOR SEQ ID NO:34: SEQUENCE CHARACTERISTICS: LENGTH: 870 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 870 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:

TTGGGTATCA

TTAAGCTTGT

GAAGAAAACA

GAGCTTAAAG

ATCCATAAGA

TCCATCTTAT

GGCGATATAG

GCTTCTCCCT

AGCGCCTTAC

TCTTTAGCTT

GACAAAGAAA

ATGTATCAAA

TTAAATTTAG

ATGCCTCCCT

TATTATATTA

ATATGTGTTC

GCGCTGAAGA

CCCCTAAAGA

AAGAAAATGA

AAAAACGCCA

TCCAACAAAT

GGATTAACGC

TGCTGTATGG

GCTTTTATGG

CTTATCAAAC

AAAGGTTTGC

ATTTAAAAGA

GGGTGAGCAT

TAAAAGAAAC

GTTACAACTA

TAAAAAAATA

AAATATCACC

CGCTCCCATT

AGTGGCAAAA

GCTTTACATG

GGCTAAAAAT

TAATCCTTAT

TTTAAGGAGC

GGAATATTTA

CGCAAGCTTG

GTTAGGGATA

GATTAGAGGG

GACGCTCAAC

TTCGCAAACC

TTTATTGTAA

AGAAATCTCA

AAAGAAAACA

CTTTTGGAAG

AAGATTGATG

CTCAAAGGGG

AAGAGCGGCT

GAGAAGTTTG

GGGTATCAAA

GGGGGGGCGA

AATATTGATC

TTTGGAGGCG

TATTCACAGC

CTCAAACACC

TTTTTATATT

TTTTATGCTT

TGACTGAAAC

AAAAACGCGC

AAAAAAGCCT

AATTGCATGA

TTTTTATAGG

AACTTTTAAG

AGTATTTCGC

TGAAAGGGTT

TGTTGATGGA

TTGGAGTGGG

CTAACGCCTT

GCTTTGAATT

ATTTTAAAAG

TGGTTTTATT

GAACACGACT

CCAAACTCTA

GCTTGAAGAA

AAAGAATGAA

CGTGATCCTT

CAATATTCAA

TAACGGGATT

TAAAAGCGAT

TAAGCCTATT

GTGGAATGGG

TGGGTTGGTG

AGCCCTAAAA

CACTAATATT

120 180 240 300 360 420 480 540 600 660 720 780 840 870 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 2007 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/18323 WO 9818323PCT/US97/19575 114- (iv) ANTI-SENSE: No 7 5 (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .2007 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAGAAAAC

GGCTTTTTCA

AAAAGACACA

ATTTTAAAAA

TCATCTTTAT

TTCTTGCCTT

ATTGATCTAG

GCGTTTGATA

AAATTTGAAG

CTCAATAACA

AACACTTGTC

CCACAAACCG

CAATCTTGGG

TGCGATAGCG

GTCGATCAAC

GAAATTGATG

AATGATGGTG

TTTGGCAACG

AGCCACACTA

AAAGATGGTC

TATAATGTGT

AATTCCATCT

GTTTGGCAGC

CAAACAAACT

AGCACCATCC

TCGCAAAGTT

TTTAATGATT

GTTAATCAAA

ATCACCACTT

TCATCTTTTG

AAAGTCAAAG

TCTAAATATT

AGCGGTGGCG

TTTTTCAATT

TATTCATCCC

TAGAAGCCGG

CCACCACAAA

GAGCGGCTAA

CCCCTGTTAG

ATAATTTAAA

GCGTGATAGA

GTTTAAAAGA

CCACTAGCAC

TTAAAACAAA

CTTACAATAA

CAGAAGAATT

GCGATGCGAT

ATCCTTCAAA

AATATATACT

CGGTTGTTTT

AATATGGCAC

ACCTTAAGAC

AAGGCTATGG

AAGTGGAAAA

GTTCGCTTTA

ATCACAATTG

AGCTCATCAA

ACAACCTAAA

AAAAAACCTT

TTAGAAGCCC

TCATAGGGTT

AAGTCCAGCA

ACTCCAATAA

GTATCTTTGG

GAAGCGGCAA

CTGTAGGGAT

ATTATACGAA

ACGGGTGGGT

ACTTTTATTA

CTTTGAAACT

AAACACTTAC

TTTATTCACC

AGTGTTGTAT

TAATGTTAAG

GACCATCCCC

GGCGTTTGAT

TTCTATTTCT

TCTTATAATG

TAATGGTAAT

CACCAATTTA

CTTAAACGCT

ATGCGTAAAT

CAACAAACAA

AAAAAATTCA

ATTAGGGGTA

TATCAATTTA

GCATAACGGG

GGATAGTAAT

TGGGGGATCC

TGCGGATGTC

TCAAAACGCC

CGCTAGTTTA

TGTAACTTCT

TATTTTAGGG

GGCTTATTAT

ATTGAGCTAT

AAATAGCCCT

GGGGTTAAGG

TTTAGATGTG

TAGCATCCCT

CTCTTTTGTT

GTTTTAG

TTCAGCGCTT

GGGCTATTAG

GCAACTTACA

AATGCCGAAG

ATGTATAATG

CTTAGTTTTA

AAACACTCTA

AAAATTGACC

GATACTAACA

AAATATAGTA

ACAAAAAATG

ATGTTGAACA

CCTTTTGAAT

CCCGGAGTAA

GGTATTATTA

GGGGTTGTAG

GAAGCCTATG

GAAGATTTAA

AATATGACCT

GGCAAGCCAA

AATCAGCCCG

CCGGCTGGCT

TTGCCGATCA.

AACACGCAAG

AGCGTTACCA

GTTAACGCTA

GGCATCATCA

GGTGGGGGGA.

ACAGGCATTC

GGCTTGTATA

GCTACCGGGT

TTAATCCAAA

TTCAATGAAG

TAGAAGCGAA

AAGGCACACA

ATTATTTACC

CGATTTCAAA

GTCAATTAAC

CAGACGCTCA

AGATTGTTTT

CCTATACTTT

CGCAGAGGGT

ATGAAAATCC

ATTGTTGGCA

TGATCGCTGT

TCACTAACAG

ATGGGCGTGT

ATAATTTTAG

GGTTAGCCAA

CTTTAGATCC

GAACCATCTT

ATCAAAGAGT

AAGATTCTGA

CTTTCCCTAG

TTTTAGGGGT

ACTACGCTAA

ATTTAGCCAA

ACCACCATTT

AAATAGGCTA

AATACAATTA

TAGATTTGTT

AAACCAAAAG

ACAGCTATTA

TGAACTACCG

GAAAAGCTAG

GGGCTAGCCA

CGAGAAAAAC

AACGCAAGAA

CACAGACACG

ATTAAAATTC

TATAGAAAAC

AGGCAACACG

ACCCGGGGAG

ATTTCTTCCA

GTTTGAAACG

AAACAATTTC

AAATTTCACC

CTTAGACTCC

CTCAACAGAT

TGATACTAAA

AAAAAAAATA

TGGATATGGC

TAAAAAACTC

GCATGAATTC

GCCGGTAACG

TGGCCTCCCC

CAACTACCCT

AACAGCAGCG

CTTGGGGAGT

TTCCATGCTC

TTCAAACGCA

TCAAAACTAC

CGCTAAAGCT

ATTGGATTTC

GAATTTTTCT

TGTGTTGAAC

CTATAAGCAT

CGTCGTTTCT

CTTTAAGGTG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2007 INFORMATION FOR SEQ ID NO:36: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 192 base pairs TYPE: nucleic acid CC) STRANDEDNESS: double TOPOLOGY: circular WO 98/18323 PCTIUS97/19575 -115- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .192 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: ATGAATACAG AAATTTTAAC CATCATGTTA GTTGTCTCCG TGCTTATGGG ATTGGTAGGC TTAATAGCGT TTTTATGGGG GGTTAAAAGC GGTCAGTTTG ACGATGAAAA ACGCATGCTT GAAAGCGTGT TGTATGACAG CGCGAGCGAC TTGAACGAAG CGATTTTACA AGAAAAACGC CAAAAGAATT AA INFORMATION FOR SEQ ID NO:37: SEQUENCE CHARACTERISTICS: LENGTH: 1221 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1221 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:

ATGGTATTTT

TTATTCCATT

CTTTTAGTGG

AACCATATCC

GAAATCCAAA

GCCCTTATCC

TTTTTAGACT

CAAACTTCGC

TTGATGAACG

GCTATCGTTT

ATGGCGATGG

TATTACGATT

TTCATAAGAA

TATCCTATGG

GTGAAAGGCT

CCCAAAAACT

GCAATGTTAC

CTATTAGCCA

TTATCCCCAT

CCTATCAAGA

CGTATAAAAA

ATACAAGGGA

TTAGCTCTCG

CAAAAGCGCA

AATTATTTTA

GGTTCTTTTA

TGTGTGGGAT

CTACTACAAT

CTACTACACT

GGATTTGCAA

TGTTTTCACT

TATTGTCAAA

AAGCGTGCCT

TTATCGTGTG

TTTGCACCAA

AGAAGTGGCA

AATTTTATCT

AA.AGCCGATG

AAGCTCACGC

TTGAGCTCTC

TTAAGAGATG

ATCCATATTT

CGTAAAGAAA

GCCACCAATG

TTTAAACGCC

GGGCAAGCGT

TACTATCTTT

GGGTTTTTAC

ATTCTTTAAT

GAATGGCTAA

TGTTAGGGTT

AAGATAAAGA

CAAATAACAC

ACAAAAAAGG

GAACCCTCCT

ACCCCCTTTT

TAGTGAAAAA

TTGGCCAGCC

TTTCCCATTC

TAGAAACCCC

GGTTGCTTTT

AAAGCAAACT

TTTAGAAAAA

ATTGAGTGCT

GCTCATTCAA

AGAGGATTAT

TCTTTCCTTA

AGCCAACCAA

CGATAAAATC

GACCATCAAA

AAACGGGCGT

GGTGAAATAC

WO 98/18323 WO 9818323PCT[US97/19575 116-

ACCCGCATTT

CCTCATTACG

GGCCGTGTGG

AATGAATTGC

TCGTTCGTTA

CCGCATTTGC

CGCACCGCTA

TATTCTAAGC

TATCTTTTAG

CTTCGCCTTT

GCGTGGATTA

GTTTTATAGG

GCTTGGTGTA

AAAAAGGGCA

ATTTTGGCGT

AAAGCAAGCT

AAAAATTAGA

AGGGTTTTTA

TTCGTATGGG

TGCGGCTAAA

GGTTAAGGCG

TGCTCACATG

AATCATAGGA

GTATAAAAAC

GCATGGCAAA

AGAACTTTTT

AGGTTC CAT C

CATGGCAGTT

GGTTATGGGA

AGCGCGTTC!G

AGAGTGGGAA

TCCCGCCCCA

CAAAGAGAGG

AAAACdCATT

CTGTTTTAAA

TGATCCATTC

AGGTGGTTGA

CTA-ACGGATT

GCACGGGTTT

TTAATCCTTT

TTTTTTTAGA

CtTTTGAAAA

AGTTAAACGG

TGCTTCAGAC

AATCCATTTG

AAAAAAAGGC

AAGCACCGGG

AGGCTATATC

AAAAGCTCAG

AAATTCATTT

780 840 900 960 1020 1080 1140 1200 1221 INFORMATION FOR SEQ ID NO:38: SEQUENCE CHARACTERISTICS: LENGTH: 891 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .891 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:

TTGTTTTTAG

TCGCAAGAGA

AAACGCCCCA

AACATGGTGT

GACAATTCTT

GAAAAAAACC

AGTCAAAAAA

GAATATTCCC

GGGGATCAAT

AACGATAAAG

CAAATTAAGG

AGGCCTTTTT

AATAAGGCTT

ACCGATAAAT

CGCTTTAAGA

TCAAAAAAAT

GCTTTATCAA

GCTATGTGGA

ATCAGCCTAT

TTAACCCTGA

TACTCTCATA

ATCCGTTCCT

AACAAGATTT

GGTTGATAGA

ATCGCCAGAT

GCAAAATTTC

ATGAATCGTT

TAGATACTAT

TAGACAGCCA

GCGATACGGA

AGGCGTGGTA

AATGCAAAAA

TTCGGATTAT

AGAGGAAAGA.

AAATTCCGTG

CCCAAACGAT

TTACA-AGCCC

CTACCCCCTA

AATCCAATCC

CCAAACTTTC

TTCGTATGTT

TTTGTTAGAA

GGAGATTTCA

GCATA.AAGCC

ACTCTTTTTA

ATAATGATTT

AAAGCCCAAG

GAAGTCTTTA

AACGCTTTTT

ATTTTACTGA

CCCAATAACA

AAAAGAAAAA

AAAAATGGGG

AAAGCCTTGA

ACTTTTAATG

TATACCACCA

AAAAAGAGCG

AAGTGTCAAA

ATCAGTATTG

TAGTCTGCTT

AGCAAGAAAA

GCGAAACGAT

TCCAACTGAC

ATGAGCCAAG

ATGAAGACAA

CAAAAAACCC

ATATTATCAT

AGCGTTTTTT

ACACTAAAAC

ATAACGGTAG

ATAATGTTTA

TGGTGTTAAA

ATTTGGATTT

TTTAGCTTGC

TGACGGCTCT

TTTTTTACAA

TAAAGATGAA

CGATAATAGT

CGCTAATAAT

AAAACTCATT

GAGTAAAGAA

AAAAGATCAA

GCAAATCGCG

CTTGAGTTTA

TACGATAGAG

AAAGCATTCA

TAAAAAAGAG

G

120 180 240 300 360 420 480 540 600 660 720 780 840 891 GAATGTCTTA AGGAAAGTTA INFORMATION FOR SEQ ID NO:39: SEQUENCE CHARACTERISTICS: LENGTH: 747 base pairs TYPE: nucleic acid STRANDEDNESS: double WO 98/18323 PCTIUS97/19575 -117- TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genoic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .747 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:

GTGAGCTATG

TATGCGACAA

GGGAATGTCC

TATTTATTGA

AACACCGATG

AGAGGCTTTA

GATGGGATTT

CGTTTAGCGT

TTCTTCTATA

GGGTTTGAAA

ATGGGGCCTT

GGCAAAAAAT

GAATTTTCTA

ACAACACCGA

TGTCTGGTTT

GTAACACCAA

TAGATTTGAT

ATTACTTGCC

GGAACGGCTC

TTACCGCTTC

GGTTTTTTGA

ACGCTCCCAC

GGGCGACTTG

TGGTGTTGAT

GTAAAGGGCT

TGGGAACAAG

TGATTATTAT

GCCAAGCTCT

AGTTTATGGT

CGCTCGTTTT

CTTAAACTCC

AATCACACCT

TACTGAATTG

CTTTGGTTTC

CACGACGGCG

GAGGGCTTCT

TTTCCCTATA

GTGCTTTAAC

GTTTTAA

TTCCCTAGAA

GGCACGCTCA

AAATTCGCCG

AAAACGCAAG

ACTTTCTACA

AAAGATGAGT

AGCTATGGGG

TTAACCTTTA

AATTTTAAAG

ACAGGCTTAC

GCGTTTTTCA

CCTAACATGA

ATGGGGTTAT

ATTCTTGGAA

CTTACCACCA

GGGGCTATAT

TGGGGGGCGT

TTGGCTTGTG

TGTTAAAAGC

AAACCCCAAC

ATTATGGCGT

AGATTGAATG

ACCAATGGGG

ACGATTACAC

CTTTAGTTCC

CGGGTTAGGC

TTTGCAAAAA

CTTTAGGTAT

AACCACGGTG

GCTTGGAGGC

GGCTAAAATG

TAGGGGGAGT

TGTAGGGGCT

GATTTCGCCC

CGATGGCAAT

GCAACATTTT

INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1008 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genoic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1008 (xi) SEQUENCE DESCRIPTION: SEQ ID GTGCAACACT TCAATTTCCT CTATAAAGAT TCTTTATTTT CTATCGCTTT ATTCACTTTC WO 98/18323 WO 9818323PCT/US97/19575 118 ATTATCGCTC TTGTGATTTT ATTAGAACAG

AAAAAATTTT

GACGAGCTTT

AAAGCGGATG

GATGAAGAAA

TTGCAGAAAA

GCGTTGTTGA

ACTTTGGAAT

TATTTAATGC

GCGTCGTTAG

TTTTGGCA.AG

ATGAATATCC

CAAGGGTTGC

CTATTGCATA

CAA.ATCTTTC

ATGGTGCTTA.

TGCAAAAATT

TAAAGCATGC

TGGAAATGAG

AA.ATCGCTGT

CAAAAGACAC

AGCTTTTGCA.

GTTTGGAAGA

ATTTAATAGA

ATTTGAAAAA

AAATTGATAC

CTGCTTTTAT

TTTTGGATCA

GCCCTATAAA

CTTTTGAA.AG

CGCCCAAAAT

TAAAATTTCC

CATTGAAATC

TTTAGATTTA

CGTGAAAGAA

TGCGTATGAA

ATTAGAGGTG

GAATAAGGAA

AATCGCTCTG

AACCGAACGG

TTTAGAAAAA

CAAACCTTGC

AGCGAGTCTG

CCATAGGTGT

GCTAGAGCGT

CAAAACGCCT

AGTTTGATGT

TTAAAAGGGC

TTGGCTAA.AA

ATTTTGCGCT

TTAGAAAAAG

CCTAAAATTG

GATGCGGCTA

AATCACTTAA

CTAGAAkAATG

CATGCCCTTT

CA.AATTTTTG

ACTTTTGAAT

CCTGTGTGTT

GCTATGGGAG

ATTTCACCCG

ATGCGAGCAG

TTTTAGCTAG,

TTTTGAATCG

ATTATTTTAG

TTTCCCCAAG

ATTATTCAAA

AAACGATTAA

AAATCTTGCA

AATCGCATGA

TGATCGATCT

TGCAGGACAT

AATTAGAGGT

ACCGCTGCA.A

ACCAGTTAGC

TGGATTAA

AAAGAGAAAC

CGAGAATTTA

GGCGTATTCT

CCCCTTAAA-A

CGTGGGGTAT

GA.ATGTGGAA

GGCTTTAGAA

AAATTACCTC

TGTTTCAAAA

TGAAAATCTT

TTTATGGGAT

CGCGCGATCT

TTTACGCGCT

GCATTGCAAA

GTTTATGGAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1008 AAATCTCTAA AAAAACGCAT INFORMATION FOR SEQ ID NO:41: SEQUENCE CHARACTERISTICS: LENGTH: 1242 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1242 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:

ATGAGGAAAA

GAGCCTGATT

AAAATCCGCC

TTGAAAAATA

CATCATGGGG

AGTA.AGGGCG

ACAACCCCTC

ATTTTTGGT.A

ATTTCATTGC

AAATCTAAAG

CAAGAAATTG

ATGATGGCGC

GGGCATTATA

CGTAATATTT

AACAAACACA

TTTTTTCTTA

CTAAAGTGGA

AAGAATTGAA

AAGAAGAAAA

ACGCCAAAJAA

TTCAAAATCA

AAGCTACTGA

ATCCTAATAA

TTGTTAATGG

TGAGTAAGGC

AGCGCTTAAA

AACAACAAGG

AACTCTATAG

TGCTCACGAA

TATTTCTAAG

AGCCTTAGAA

GAGTAAGGAA

GAAAGAAACA

TCCCACTCCA

AGGCGTtCAA

AAAAAATAAG

CGCTACCAAC

TTCGCCTATC

TCAAGCTAGG

AATCCATGTA

CATGGATTTA

AGATCAACTT

TGTGGATACC

GTTCTATTAT

GGGAGGAAGC

TTGAAGAATA

AAAGCCAAGA

AAGATCACGC

AACAACGCGC

GAAACAAGCC

AACACCCTTG

ACGCTGTATC

GATCGTTTGA

GATGATGACA

GACCATTTCA

AAAGAGCATT

AGCTCTGAA.A

TTATTGGGGT

AAGAGTCTTC

AGGAATTAAA

GAAAACCCAG

CTCCTAAA.AT

CAAAACCTGA

CTAGCTCTCA

AAGATAAGGT

AAATCCAAGA

TCGCTGAACG

AGCTAGACCA

AACAGATGCT

TAGAAATGCA

CCAAAATGCG

AA.ACCGTGCG

GGTTTATGCA

TTTGGATAAA

GAATAAGGAT

AGCAGAAGTC

CAAAGGGAGT

AGAAAAAGAT

AT TCAATTC C

CGTAGGGGGC

AGAGCAAGA-A

CATTAAAAAC

AGAAATGGCG

TATGGCTGAG

AGAATTGTTG

CGAATATTAC

CTACACTTCC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 AGGAGCAATT CAGTATCCCC ACAGAAATAG WO 98/18323 WO 9818323PCTIUS97/19575 119-

ACCAATCAAG

AGTAAGGCCA

ATTTCGCATG

ACCTTTTATA

TTCATCGCCC

AAATTGCGCG

AGGATTTAGA

ATGAAAAAAT

AGCAAGGCTC

TCAAGGAAAA

AAAAATTAGT

TTAAGTCTAG

AAGGGCTATG

AGAGATGAAA

TTTCACGCCC

AAGGGGTAAA

GGAAGAATCT

GATTGTGATG

GCAGACCCTA

ACCCTAAACC

GTTATGAATG

AATGAAGTGA

AAGGATAAGA

ATCAGAGAGT

ATTTGGAAGT

CTCAAATCGC

GGGGTGGGGG

GCTTCAGTCA

TTTTAGAAGA

GA

CCCAGGGGTG

CCAAGTCTTT

GCAGTTCATC

GGCCAAGCAA

GCATTTTGAA

960 1020 1080 1140 1200 1242 INFORMATION FOR SEQ ID NO:42: SEQUENCE CHARACTERISTICS: LENGTH: 561 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .561 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: ATGATTAAAA GAATTGCTTG TATTTTAAGC TTGAGCGCGA GTTTAGCGTT

GTGAATGGGT

AATTACTCTG

GTAGGCTTTG

ACTTCAGGGA

ATTGTCAATC

GCCGGAAACA

AATTTAGGCG

CCTATGGTTA

TTTTCATGGG

ATTGGCGTCA

CCAATAAATG

CTGAACACAC

TCATTCCTTT

CTTGGATGTT

GAAGAATGCG

ATCAGGGTAG

TGCGGGTTAT

TGGCAATGAC

GTTTGGGGCT

CAAAACCAAT

GGATAAATTC

CCCTTATGAT

TGTTGGGGAT

CAAAGATGTA

CAACAAGGTC

CTTTATGGTT

AGGGTGTATG

TTGCTCACCT

GCTCTAGGTC

GTCAATCAAA

CGCAGTGCGT

GGGCTTATCC

GTTATGGCCC

TGAATTTCAA

GCTTTTTAGA

ATGGCGGCGG

TCATTGGTGG

CCAGATTCCA

TTGAAGCGGG

GCTACTATTC

AGCTGGCGAA

TTATAACAGC

ATTAGGTTTT

TTGGTTTAAC

TGGCGATTTG

CGTTCAATTA

GTTCTTATGG

CGTGAAATTC

TTGGTATGTG

120 180 240 300 360 420 480 540 GATTATGTCT TCACTTTCTA G INFORMATION FOR SEQ ID NO:43: Wi SEQUENCE CHARACTERISTICS: LENGTH: 729 base Pairs TYPE: nucleic a'cid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/18323 120 (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 729 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: PCTIUS97/19575 5

ATGAAAAAAT

GGCATGGATG

CATGCGGATA

CTCTTGGGGT

GACTACGCTC

CAAGTGGCTA

CCCAGAACTT

GTCATCAATA

TCATGGCTTA

AAGAAAGCCA

CATTCTAGCA

GCAAAAAATT

ACTTTCTAG

TTTTTTCTCA

GTAATGGCGT

TTAATTCTCA

ATCAATTTTT

ATGCCAATTC

GTCAAATTCT

TTGAGCCGAA

ACGGCATCAT

TGGCGACACC

CTTCTTTCCA

TTGAAGCGGG

TGGATATAGG

ATCTTTGTTA.

TTTTTTAGGG

AAAACAAGCC

CTTTGAAAAA

TATTAAGCTT

TGGGAAACA

CATGCTCACT

GAGTTTGGGG

GAGCTTTGAG

ATTTTTATTC

CGTGAAATTC

GTTTAGGCGC

GCTCTTATTA

GCGGGTTATT

ACCAACGCTA

CACTTTGGCT

AAAAACCCTA

GAAATCAATC

TATGGGGGGG

GCTTTTGGCG

GGCATTTTAG

AATGTGGGGG

CCCATGCTAA

GTGTATTCGT

TCTCTATGAA

TGCAAGGACA

CGATCAAAGG

TACGCCTTTA

ACTATAATAG

GTTTAACAAA

CTATGGACGT

GGATACAATT

TGGAACAAGC

CTCGCTTAAG

AGAAAAACCC

GGTATGTGAA

TGCGGTATCT

GGCGCAAATG

CTTTGACGCG

TGGGTTTTTT

CGAAGCGGCG

CATTGCCGAT

GATGGTTAAT

GGCCGGCAAT

CCTTGTGAGC

GATCTTAAAA

CTACATCACT

TTACGTGTTC

1.20 180 240 300 360 420 480 540 600 660 720 729 INFORMATION FOR SEQ ID NO:44: SEQUENCE CHARACTERISTICS: LENGTH: 772. base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 2 .771 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:

ATGGGATACG

ACCCTTGGTG

TATAATAATA

GAGTCGCTTG

GATTACAAGA

TATAACAATT

GCGGTGGAAT

GGCATCATGT

TTTAGAAAAG

CAAGCAAATT

CAGAACACCT

AGGAATATGA

CTTATATTCT

AAGCGGTTGA

TGGGCGTGAT

ATTTTAGAAT

ATATGGAGGG

CGATGCATAA

AGCTTTAAAG

TGAGCAAAAA

GCGAGCGGCT

TTTAGGGATC

ATATTTCCAA

GTATAAAGAG

AGCTACAGAG

CAGGGGAGTT

GGGCAATGTG

ATTTGTTTGG

GGGAATTATA

TCTTTTTATA

ATGTATGAAA

AAAGCTGTTG

GGTAAGGGAG

AAAGGTTATA

CCAAGTAACT

GAAGCTTATA

TAGGTTTATG

TTTATAAGGG

AGAGCGCTAT

ATGGTAGGGG

ATAACGATAT

TTCCTAAAGA

CTAACGCTTA

ATGCGAAAGC

TTCTCCTAGG

TTTATTTAGC

AGAGGAGGCT

TAAAAATGGT

TGTACCTAAA

ACCTAGAGGG

TGAAAAGAAA

TATCAACTTA

GACAGAATGT

GGATATTTAT

WO 98/18323 WO 9818323PCTIUS97/19575 121

TATAGCGGGA

AAAATGGCGG

TATGGGTTAG

GATTTTGACA

ATGATCAATT GGGTATTGAG CCGGACAALAG ATAAGGCTGT TGTCTATTAT CTGATGTGAG TTCTTCTAGA GCTTATGAAG GGTTGTCAGA GTCTTATCGG GCGTGGAAAA AGATAAAAAA AAGGCTGAAG AATACATGCA AAAAGCATGC TTGATAAAAA TTGTAAGAAA AAGAACACTT CAAGCCGATA A INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1974 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1974 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAGAAAAC

GGCTTTTTCA

AAAAGACACA

ATTTTAAAAA

TCATCTTTAT

TTCTTGCCTT

ATCGATCTAG

GCATTTGATA

AGCACTTCTA

ACAAATTTGG

GAAGCCTTTA

GTTTTAGACT

AGCCCAACAG

GTCAATTCTA

AAAAACAAAG

AGTGATATTA

GCTTCTGCTT

GATTTAAGAA

ATGACCTATC

AAGCCAAAAG

CAGCCCGCTT

GCTGGCTTTT

CCGATCAACT

ACGCAAGATT

GTTACCAACC

AACGCTAAAA

ATCATCAAAT

TATTCATCCC

TAGAAGCCGG

CCACCACAAA

GAGCGGCTAA

CCCCTGTTAG

ATAATTTAAA

GCGTGATAGA

GTCTAAAAAT

TTTCTGACGC

TCGTAAATTA

CCCCACAAAC

CCCAATCTTG

ATTGCGATAA

AAGTCGATCA

CGGATCTTGA

CCCCTAGCAA

TAGATCCTAA

CCATCTTGCA

AAAGAGTGCC

ATTCTGATGG

TCCCTAGCAA

TAGGGGTAAC

ACGCTAACTT

TAGCCAATTC

ACCATTTTTC

TAGGCTATCA

ACAATTACGC

ACTTTTATTA

CTTTGAAACT

AAACACTTAC

TTTATTCACC

AGTGTTGTAT

TAATGTTAAG

GACTATCCCC

TGACCCCTAT

TAACACGCAG

TAGGAATGAA

CGCAGAAGAA

GGGCGATGCG

TGATCCTTCA

AAAATATGTG

TGTAATTGTT

CAATGATGAT

AAAACTCTTT

TGAATTCtAGC

GGTAACGAAA

CCTCCCCTAT

CTACCCTAAT

AGCAGCGGTT

GGGGAGTCAA

CATGCTCAGC

AAACGCATCG

AAACTACTTT

TAAAGCTGTT

TTCAGCGCTT

GGGCTATTAG

GCALACTTACA

AATGCCGAAG

ATGTATAATG

CTTAGTTTTA

AAACACTCTA

ACTTTATTTC

AGGGTGTTTG

AACAAATTTA

TTCACTAATT

ATCTTAAACG

AA.ATGCGTAA

TTAAACAAAC

TTAAAGGATT

GGCAAGCATT

GGCGATAACC

CACACTAAAG

GATGGTCAAG

AATGTGTGTT

TCCATCTATC

TGGCAGCAGC

ACAAACTACA

ACCATCCAAA

CAAAGTTTTA

AATGATTTCA

AATCAAAAAG

TAGAAGCGAA

AAGGCACACA

ATTATTTACC

CGATTTCAAA

GTCAATTAAC

CAGACGCTCA

AGATTGTTTT

TTCCAAAAAT

AAACGCTCAA

AAGATCACGA

TAATGTTGAA

C!TCCTTTTGA

ATCCTGGGAC

AAGACATTGT

CAGGGGTTGT

ATGGCCAGTT

TTAAGACTAT

GCTATGGGCA

TGGAAAAGGA

CGCTTTATGG

ACAATTGTGC

TCATCAATCA

ACCTAAACGC

AAACCTTTGT

GAAGCCCTAT

TAGGGTTGGC

TCCAGCAATT

CGAGAAAAAC

AACGCAAGAA

CACAGACACG

ATTAAAATTC

TATAGAAAAC

AGGCAATGTG

GCCCGGAGAG

TGAAGCCACT

TAAGATTAAG

AAATCATTGG

CATGATCGCT

GTTCACTAAC

AAACGGGCTT

CAATAAATTT

AGGGCTTGGG

AGGGGTAGTA

CAATTTAGAG

TAACGGGAAT

TAGTAATGGC

GGGATCCAAT

GGATGTCCCG

AAACGCCTTG

TAGTTTAAAC

AACTTCTAGC

TTTAGGGGTT

TTATTATGGC

GAGCTATGGT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 WO 98/18323 WO 9818323PCTIUS97/19575 122-

GGGGGGATAG

GGCATTCAAA

TTGTATAACA

ACCGGGTTGA

ATCCAAAGAA

AATGAAGGGG

ATTTGTTATT

CCAAAAGGAA

GCTATTATGT

ACTACCGCTA

AAGCTAGCGT

CTAGCCACTT

GGATTTCATC

TTTTTCTTCA

GTTGAACAAA

TAAGCATTCT

CGTTTCTAGC

TAAGGTGTTT

ACCACTTACT

TCTTTTGGTA

GTCA)AAGGAA

AAATATTCTG

GGTGGCGATT

TTCAATTACG

CCAATAAAAA

TCTTTGGGGG

GCGGCAATTT

TAGGGATTAG

ATACGAACTC

GGTGGGTGTT

TAGCCCTACA

GTTAAGGGGC

AGATGTGGCT

CATCCCTTTA

TTTTGTTTTC

TTAG

1680 1740 1800 1860 1920 1974 INFORMATION FOR SEQ ID NO:46: SEQUENCE CHARACTERISTICS: LENGTH: 504 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 .504 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:

ATGAAATTGG

TTGCCTGGAG,

TTTGAGCATA

AAAAAAGACA

TTTTTAAGCG

TTTTATGACG

TTCACTTCAA

AGCGATGAAG

TGAGTCTTAT

TTTATCAAAC

ACGGGAAGTT

AACTCAATCC

ATTTGATTAA

GCAAGACCTA

GCTATGACAA

AAATCAAAAA

TGTAGCGTTA

TCAAGAATTT

CTATGCCTAT

TAACCCAAAG

GGTTGGGGAA

CCATGTGAGA

ATGGGGGTAT

TCTAAAGCTC

GTTTTTTGTT

TTATACATGA

GGTATTTCTG

CTAAGGAATC

CAATCTTATA

GTCACTCAAA

GTGGGCAAAA

AAGCGTTTTA

GTTTTTTAGG

AAAGCTCTTT

ATGTGGATGG

GCAGCGATAA

AAGGCGGTAA

ATTCAAACGG

CCTTCACCTG

ACTTGGACGA

GGCTGTAGAG

TGTGGAGTTT

CTCTAAAGCC

AGGCGTGGTG

GGCGTATAAT

GGATTTGGAA

GAAACGCCTG

AGTCCTTAAA

120 180 240 300 360 420 480 504 ACCCTCAAAG ATAGCCCTAT TTAA INFORMATION FOR SEQ ID NO:47: SEQUENCE CHARACTERISTICS: LENGTH: 885 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/18323 WO 9818323PCTIUS97/19575 123 ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. 885 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:

ATGAGTAATC

TTTGATAATA

AAATCCAACA

GTATTTGATG

AAAAATATCT

GAACCCGGGC

GGCGCGGAAG

ATTGTGATTG

GATTGCGTGG

ATTAAAATCA

CCTAAAGAAG

TCATTAGAAT

AGGGAGCGAA

CAGATAGCGA

GGTTTAAAAA

AAGCGAGCCA

AGGGGAATAC

TTAGCGCTAA

CGGATATTGG

TGCATGCCTT

TTTGCTTAAT

CTTTGGATCG

ATACGGGTGC

TGATTGTTAC

ACTCCAAGAA

GCAGGGCGAC

TGCACTATTT

AGATTTTGAG

GCCTTTTAGT

TTTGGATAAT

CAAATTCATC

TTTAGCTTAC

TTTAGCGAAT

AAAAGGCGAA

CCCTGGGGAT

ATTCGTAGAT

TGGGATTGGG

CACACCCGAT

TAAAGATGAA:

TTATGAAAGG

AGGGGCGATT

GAAAATAGCC

TTCTAAACTA

TTTATGAACG

GCTATCACAA

TCTTTATACA

TTAGATGTCA

GCCAAATTGC

AGCGGCGAAG

GAAGAGGGGG

GCCACTACGC

CCTTCAGCGA

TTGTTCCTTA

CTATTCAAGG

GAAPACAGCT

CCTAACGATT

GAAACCGGCA

CTAAAAATCC

GCGGTAAGGG

AGAAAGGTTA

TTTTTGGGGT

AAGAAATCAT

AAATTTTAAA

TTTTAAGCTC

AAGCGTTTTT

TTACCGATGC

TCGCTAACAT

TGGCTAAAAA

CCTTATTGAA

TGTTTTCGCA

CTTTAGAAAT

CAAAAGTTTT

GGGCGTGGGG

TAAGGTAGGG

GAAAAC CCAT

TTGCGAGATT

ATACATCAGC

TTTAGATTAT

GAATGCGAGC

GTATGCATGC

GGTAGCCCAA

CAATATCGCT

ACGCTATGTG

ATCCATTGAC

ACCAAAAGAA

GCTTTTTTAA AAGGCTTTTG AAGTATTTGG GGTAG INFORMATION FOR SEQ ID NO:48: SEQUENCE CHARACTERISTICS: LENGTH: 1119 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1119 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:

TTGGAACCTT

TTGTTTTTAA

CTTGTCACTC

TTAAGCGCGC

TTTAGCGGCA

AAGACTAATC

TCGCATGAAT

TTGTTGTTTG

CAAGAAATCG

TTATAATGAA

AAACCCCCCC

ATGCGAGCTC

CTAAAGAAGG

GCTGGAGCGA

ACATCAAAAA

TCGTAGGGGT

CCTAAAACAT

GCACCAAACC

CTATTTCACG

TTTAATCAGC

GGCAAGGGAT

AGCCTTCATT

ATTAGGTAAC

GAGCATGGGC

GCCGCCTTTT

TCCCCCTATG

CAACTCACTA

TTGCCTAACG

GTGAAAATCA

CTTTTAACCA

CCCTTGCTTT

GGGTGGGCCA

TTGTGGGGCT

CTTTCACGCA

TCCCTAAACC

ACAATCTTTT

GCGCGAATCT

AAGAAGAGCT

TTTTGCATGA

CTTCTAAAAT

TTTTATCGTT

TAATCAAGCC

AAATGACGCT

GAGCGCTTAT

TTTTGACAGC

TTCTCATCAT

TAATAAAATT

CTATCAATTT

WO 98/18323 WO 9818323PCT/US97/19575 124

GAAAGCGCTT

TTAAATTTGA

CTACCACTCT

AATAACCCAA

ACCCCCTTTA

ATGCTAGAAA

AACTTAGATG

CCTAGCGATT

TCGTTTAAA.A

CTTAATCCGC

CGTTTCAATA

TAGAGCCGAT

GCCATTTAGT

ATCACGAATT

GAGAGCTTTT

AAGACTGCGC

CCTGTAAAAC

ATTCTTTAA.A

TATCACTGCG

CCTTAAA.AGT

ATTTTATAGA

TGGCTTATTT

TCATTTTAAG

AAGGAATAAG

AGCCACCCAA

AAGGCCTAAT

TGTCATGGCG

CCCCACTGAT

TTTACTCAAT

TCGTAAAGAA

TTTGGATAAA

TATTGTCTAT

AAATTCCCTT

TTTGCGCGAA

CCTTTA-AACA

TACCCCTTGT

ACCTTAAACC

TTTAGA-AACC

TGGCAAAAAC

TTAAATGGAA

CTTTGGCTTT

GCGAATGAAG

ACTTACAACC

CTCAAGTGA

AACTCTCTTT

CCACTGATGG

TGTTGAAATT

ACCAGCTCCA

ATTCTTTTAA

CCATTTCTAC

TATTGTATTT

CTAAATTAGA

TGAGTTACCC

GCTCTCATAT

AAGCCCTTTT

CGGGTTTATG

TGACCAACAA

ACCAAGCTTA

AGATAGCCTC

AAATCTTAAA

GATCCACAAC

AAACTCCAAC

AAGCTATAGC

CAAACACATC

540 600 660 720 780 840 900 960 1020 1080 1119 INFORMATION FOR SEQ ID NO:49: SEQUENCE CHARACTERISTICS: LENGTH: 2937 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .2937 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:

ATGAAGAAAA

GTATTCACTC

TTAAAAATTG

TTGGAAGTTG

TTAGAAGTTT

GAAAAACTTA

GATGGGAATA

GATAAAAATA

GATGGCAACG

CCCTTAGTTG

GAATTAAAAA

CGCCAATCGC

AAGATTGATA

TTGGAAAATT

TTATCGCCCA

CAGCCCCAAA

AATTTGTTAG

GATAGCATTA

ATGCCATCTA

TTTAGCGTTC

GAAAACATGT

TTTTAGTCGT

GAAAACTTGG

AGCGGGTTGA

CTGATTTGAT

AAGTCAAAGA

AATACGAGTT

TCAAGCTTAA

CCCACTATTC

AACCCAGCGC

TTAACACTTC

AAAAAAATTT

ACGCTTTAAT

CTGTAGTTAA

TTAAAATGGA

AAATCACTTA

AAGCCCCTAA

AGGATTTATT

GCGCGGATTT

AAGGCAGCGT

ATCCAAGAAA

CATTCACAAA

CATTTCTGAA

TCTCTCTTCT

TAAAAATATC

AATCATTTTA

AGAATTTCCA

AATCATCAAT

ACCCAAAGCC

TGCAATTTAT

TCCAATGAAA

AAAAACGTGG

CAAGGCTAAT

AGCCACTTTG

TAAAACCGAA

TGAAACCATG

GTTGGAGGTT

GAGCGCTTAT

GAAGCTCACT

TAATTTGCAA

GTGTTTA.ATG

ACCCTTTCAA

TTATACTTAA

TTCTTCCATC

CGTTATGGCA

GACGATAAAA

GGAATCAAAG

TTGCTTTTTA

AGGAAAATGG

TTGCA.AGGGC

AGCCTAGCGT

ATTTTTGACA

TTCACTCCTA

ATTAAGCCTT

TTGATTTTCA

GAATTAACCG

TTTTTAAAAA

AAAGTCGTTT

TTGCAATTCT

GAAGGCACTT

TCATTATCTT

ACGGCATTCA

AACTCAATAA

AAAAACCCAC

TTTGGGCGGT

ATAAAGCCAA

GGGAATTTTC

AAGATGTTAA

CGTTCAATTT

TAACCGATTT

TTTTAAAGCC

AGATCCAATT

GCGAGTTTAT

CAGTCGTTTT

AAAACAAACA

GCTCTTACGC

CGACCCCTAA

TACCTTTGGA

TAAAAAACAC

TCTCGCTCTA

GTTTGTGGCA

CATACAAAAT

CAAGCTTTCT

TAAAA.AGCGT

GTCTTATTTT

TATCTTTTTT

CCTAGAAGAC

AGTCCA.AGTG

GATTGTCAAG

AAAAACCATA

TCTTTTCCAA

TGCCAGCTTT

CCCATCGCTT

TAATGATGGC

GCTCCTCATA

CACTTTTTCC

TTATTATGGC

TAAAATCAGC

CGCCCCCTTA

TAATATCCCC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 WO 98/18323 WO 9818323PCTIUS97/19575 125

CTTTACACGC

ATAGACACGA

GATTTAGGTC

AATAACAATA

AACTTTACTT

GTTTTTAGAA

GATGTTTTTT

AACCCCGATC

AACGCCTATA

GACTATATTG

GATTTTTTTG

TTTGATTCTT

AGCAAAAGCA

GATTTGAGTA

AAAGAACGAA

GCCAAACAAC

AAAGATGTCG

GCTCAAGACG

TTAGTGCATG

ATTCTTCAAA.

CAGGTTTTCA

CAAAACATGG

TTAGGGGCTA

TATTTAGGGT

ATCATTGAAT

TTGAGTAATG

AAAATCACCA

TTAGCGTCAG

GACATCATCG

AAAGCGCTCA

TCCACACGCG

AAAAAAACCT

TCAACATGCG

TGGATCTAAA

GAAAAATCAT

ACGCCACAGG

ACATACAATG

CTTTTAAGAT

CCCTAAAAGA

CTAAAGATTT

TTTCTTTATT

TAT CCATAAA

TTGATGATTT

AAGAAAAGCC

GCTATGAAAA

TGCTGATCTA

ATAGGGTGAA

GGGCTTTGTA

AAGATTTCGT

ATGGCGAATT

TCAATCTCAT

ATGGCTATCA

TAGAAAAAAT

TAGACAAAAA

TCTTAAATAA

CTAACGTGAA

ATATTATCCA

TGGATGAAGT

AATCAATTTG

CTATGCAAAC

TTCTTTGGAT

CTCTTATGAT

AAGCTTGCAT

AGACACCATT

AGACACTCTC

GAGCGTGCCA

CAAAGATTTG

CGGCTCTTTA

GAAAATCAAC

TGGCTCTATC

AGTTAAGGGG

CTTGGATAGT

TAGCTCTAAA

AGCCCACAAA

TAAAAAAATG

AATTGATGGC

TCTTAAGGCT

AGAAGGAGGC

GAAATTCCAA

CAACACCATT

AATCAAAACC

TGATCTTGTC

CAAATTAGAT

AATCCCTATC

TGTCAAAGGC

AGCGCCTTTT

CAAGAAAAAC

GACATCGCCC

ATGCTGGATT

TCTTTAGTCC

CCCAATAACA

TCTATCATTC

AAAGCCCAAA~

AAAAGCCTGT

CAACttTTAT

AAAAAGATCA

GAGGTTTCTA

CTCCCCATTT

AATAAAGATG

GATCAAAAGG

AAAATGCCAG

GAAATCCAAG

ATTATCCCCA

CCTTTTCCTT

AATTATAAAA

CATAATTTTA

TTATTCACGC

AACACAAGCT

C CCTC C CTCA

GGCTCCGTTG

GGCAAAACGC

TTAAACTTAG

GTGGGCTATC

ACGTTGGATA

AAAATCTTAC

ATTGATTCAA

AAGAATACCA

TAGACGCTAA

ATAAAATCCA

CTCAAGAAGA

AAGAGGGTGA

GCGAAGATAA

CGTTGAGTTT

TAGAAGGCGA

AGCCCTATTC

CGAGCGATTT

ATAGGAGCGA

AAATTTCTGT

ATATTACCCT

CTATTGCGGG

ATGAAGATGT

TCTCTACACG

TAGAAAATCT

ACGCCATGAT

GCGGGGATTA

TTATTGGGGC

TAAAGAATTT

TTGTCTTTAG

TGTTTGGGAT

TTGATATTGC

AAGTTTCCAC

TCGTTTTAGG

AGCCTAAAAC

GCCGTATTTT

AAAGGAAATT

ATACATCTAC

AATCGCTTTA

AGTCAATACC

TCCGCAAACT

AAATTCAGAA

ATTCACTAAA

TGATTTTTCC

ATTTAAAGAT

CCCCATTATG

TGTCAATATT

TGGATCGCAT

CTATACTCCA

TAATAACATT

ATTATTCTCA

TTTCATTAGC

CATCCATGCT

TGATATTGTC

CATGGCGGAT

TATCAACACC

TCTTGAAGAT

CGCCCTCATG

AAACCCTCAT

CACTAAAGAA

TGGCAATGGA.

TATCAAGGCT

AAAAGGAGGT

CCAAGTAACT

CACGCCTATT

AAAATGA

1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2937 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1434 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: No (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helitobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 1434 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGAATACTA TTATAAGATA TGCGAGTTTA TGGGGCTTGT GTATTACTCT AACTCTAGCG CAAACCCCCT CTAAAACCCC TGATGAAATC AAGCAAATCC TTAACAATTA TAGCCATAAG WO 98/18323 WO 9818323PCTIUS97/19575 126-

AATTTAA.AGC

TCGCCTAAAG

GATAAAGCCG

CAAGCGCAAG

TTTTTGCCTA

TATAAGCATT

TTTAGCAATG

TTAGAATATA

AACAATCTCG

AAAAGGGTTA

AAAGCGCAAG

AACCGCTTGA

ATTGATGCGC

ATTTCTGCAC

GACTCATGGC

TACCCAGGTC

GGGTTGAGCT

GCGTATAAAA

GCCAGAGCTA

AATATTAAAA

ACCACGCGCT

AAAGCCAATT

TCATTGATCC

AAACAGCGAC

CTTTGGGGCT

AACTCAGTGT

CTTTGAAC!GC

ATAACACCCA

TGAATAATGT

GCCGCCAAAG

CTCGCATGAT

CTAAGCTCTA

GGAATTTGAG

CTTTAGAATA

CTAATTTGCA

TCAGATACCA

TTTTTTGGAT

AGCAAAATAC

TGCAAAAACA

AATTGGAGCA

AGATTGAATC

GGAAATACGA

TTGATGCAGA

ACATTTTTAA

GCCGACAAGT

CACGATCAAT

TTATGAATTG

CAAGCAAGCG

GAGTTATAAT

ACAACTCCAA

CAAAGAAAAG

CGTGTATTTG

CGCTTTGCA.A

TGACAAAGGG

CGAATACGAT

CCTCACTAAC

ATTAAGAGAA

AAACAAGCAA

CCAAAAACCC

GGCTGGGGTT

ATCCATCATG

AGAAAAAGAC

TTCAAAGGCT

CGCTAATTTA

AGTGGCTTAC

CAGCGGGCAT

TCTTTAGAAG

CAAGAGATCG

CTAAAGGGGG

ATGAAGAACC

TTTAAAAATG

GCTCAAGTCA

TCTGCGACTT

CAAGTGGTGC!

AAGAAATTAG

CTGACCACGA

ATTTTGGACA

CTCAGTGTGA

AGGCAGGATT

CTCAATTATT

GCTTATGCCA

ACTGCGACTT

CTAGGCCAAT

GAACAGCTTT

AGTTTGGATG

GTGGATTTCA

AATTTAGCGC

AAAATAGACG

CGACACCGGG

CTAAATACCA

CTACCACCAA

ACACCATCGC

AAGCTAGGGA

CATTGAATGT

ACCGATCCAC

AACAATACTA

AGCAAATCCA

TTGATGATTT

TGCAATTTGC

AAAATTTGAA

TGGTTTCTTT

ACCCCAAGAT

CAGGGCGTTT

TGAATATTTT

TAGCGAATGA

ACAGAAAGTC

CGGCCAATCT

CTACCTATTT

TCAACAATTA

ACTATGTGCA

TTTTTTACCC

TGAAAAAAGC

TCTCAGTTTG

CAAAGCGATG

TACTCCAGAA

GTTTAATGGC

TGTGGCTA.AT

CGAGTATTTT

AACGGACATT

ACAAAGCTTA

TTTGGAGCAA

AAAGACCACG

AAGGGAGCAG

AGATGTGTTT

TGGGAATTTC

TGATGATATA

AAAGAATTTA

GCTTGATATT

TTCTTTTGCC

AAGGGGCTTA

CGAAGTGCA.A

TTAA

180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1434 INFORMATION FOR SEQ ID NO:51: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 1239 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. 1239 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:

ATGCTATCTT

TTGTTACTGC

AAATACCTTT

TCTCAAGAAA

GCTAACGTGA

TTGTCTCAAA

GAAAAACAAA

ATGATAAACG

ATTAAAAATT

TTATAAGCGC

TTTTTAGTTT

CTAAAAATCA

AAGTCGTTAG

GCGATTTTTT

AAGTGGATTT

AAAAAATATT

GCATTGAAAA

TAGAAAACAC

GTTTGATAAA

GGGTTTGGCT

AAAAATACAA

CAAATGGGAT

CAGGCTGGAT

AAATGGTAAA

AGAGCTTAAA

CTATAAAAAC

CCTCTATCAA

AGGGGCGTTT

AAAGATTTAG

GCCCTACAGG

AACCCTATTT

AGCACCTTA.A

AAACTCACGC

AAAACCAAGC

CAACAAGAAA

GCCAACCATT

CAATACGCCT

AA.ATCCAAAC

AGCAAATTGA

TGTATTTAGG

TGCAAAACAT

AGTCTAAAAT

AGCAATTGGT

TAGAGCTTTT

CCAGTTCGCC

TCTAACAGCC

TTTTGTGGCT

CGCTTTAGAT

CTATAACAAC

GAGCTTGGGT

GATCAATTTA

GATTAATTTA

AAACACAGCG

CGATTTAATA

120 180 240 300 360 420 480 540 WO 98/18323 WO 9818323PCT/US97/19575 127

GCGATCGCCA

GTAGCGCTCT

TTAAGCATTG

GCCACTAATT

ACTCTGGCTA

TCCAAACAAT

TATGGCAAGC

GAAGTGGAAA

GAAACCTTGC

GCGCAAATTT

TTGAATGACA

GCTTATTTGT

AGTTAGAAAT

CTAGCAGCCA

CCCCTAAAAA

ACGATATTGC

AAAAAAGCTT

ACTATAACTA

AGGCTAAATT

ACGCCAAAAA

AAAAAAACCT

ATGCGCTTG.A

AAATCACTAT

CCTTACAAAA

TTTAAA.ATCG

TTATTCCATG

TTTTGA.ATTC

GATCGCCAGG

TTTAGAAGAC

CGACATGTTT

AGTGGAGCAA

CAAAACGCGC

GGAATCGATC

TTTGAAAACT

TCAAATCACC

TCTCAAAGGA

CTATTAGAAA

GGCGAATTGA

AATAACGAGC

CTTGATGAAG

ATAAACGTTA

AGCGTCGCTT

AAGAAAAAAG

CACCTGGCCC

AATAAAATCA

AATGGCGATT

CAGCTTGAAA

TTAGAATGA

TCCAAAAAAA

CTTTTAAAGA

AAGAGCTGCA

AAAAAGCACA

CCGGGGTGTA

TGTCTATCCC

AAAGCTTGGC

TAAAACTCCT

TCAAACAGAA

ACAACGCTTA

CCTTAAGCGC

CGATTTAGAA

AAACGAGATT

TAACATTAGC

AAAAGACATC

TTATTTCCGC

TTTACCTCTT

GTTTAAAAGC

TAAAAAATTA

TGAAAAAATC

TTACAACGCC

TCTAAATAGT

600 660 720 780 840 900 960 1020 1080 1140 1200 1239 INFORMATION FOR SEQ ID NO:52: SEQUENCE CHARACTERISTICS: LENGTH: 414 base pairs TYPE: nucleic acid STRANDflEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .414 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:

ATGCGTATAG

GCGGATTTAG

CATAAAAACC

AAAAATAGCG

AAAAGCGATA

ATGCCGATTG

AGCAAAAAAA

TTAGAAATTT

AAACCGGAAC

ATGGCTCAGA

GATTAGAAGG

AAAAGTTTTA

TGAATTTCAA

CCCAATACAT

ATTTCTTGTA

CAAAAACGAC

AACCGAGACT

CGTGGATTTA

TAAACAACTC

TAAAGCCCTA

GGACGGCGGG

TCGTTTGTGG

AAAAAGAGCG

AAAAACGATA

GAAAAAAGCC

GCTAAAAACA

TCTTTTGGGC

TTGATGATGC

CGTATAGTAG

GTAAAAAATT

AAAAGCTTTA

CTAACCTTAA

ATATCGCTGA

CTTATTTTGA

ACATCCGTTT

TGCGTTCGCA

TTACAAACTC

TGATTTCACT

AAGCCATAAA

AGGGGTGAGC

AAGGACTAAA

TTAA

120 180 240 300 360 414 INFORMATION FOR SEQ ID NO:53: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 930 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/18323 PCT[US97/19575 -128- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .930 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:

TTGATGCCAC

AAATTTTCTA

GTGGGGCTTG

GAGAGGAATG

AAAGAGATTA

GAATCCTTGA

GATTTAGAAA

ATGCCCCTAA

AAGATTAAGG

GCGAGCGCTG

TTGGTGCGCA

AATGTGCAGC

GGTAATAGCG

GCAGAAAAAT

TTTATTGAAT

GTGGATAAAG

AAAACCAGCT

AAAATTTAAA

GCGTGGGGTT

CGGTTTTAAG

AAAACAAGCG

TTGAAATCAA

ATTTGAGCTT

AAACTTATAG

GCGTTGAATC

ATGGGATTGT

TTGAACATGC

CTAAAAGCTT

GCGGCGAAAA

TCCTAGCATG

GGAAGAATCT

ACACCTTAAA

TGTGATCACC

ACGCAACCTC

TTTAAAATTT

GGATTTTAGG

AGAAGAGCTT

AAAGGGGGCT

AAATCAAAAA

CGCTATCAAA

CGGGATCGAT

GGATTTTGTG

GTTTGGTTTC

CATCCAAAAA

ATTGCATTAT

GGATTTGGAT

GTTTTGGGTT

AGGTCAGTAG

ATCATTGATG

ATCATTTCTG

TTAATCGCTA

GGTTTGTATC

TTTATTGTGG

AATGGGGGAG

CATTTAGCAC

CCCACTAAAG

TTTATCGCGC

AAGACTCGTT

AGCTCCATTT

GGGCAGTTGA

GAAGTGCGGT

CATTTTCAAA

TTAGAAGACA

AATCAGGCTC

TTGTCATTCT

AA.ATGGATAC

AAAAAAATTA

GGCAAAAGAT

GGCATCTCTA

TCATGCTCAT

AAAGGAACCA

CATTGAACAC

CTAATGCGGG

ATACGCACTT

TTGGCTATAG

TTTTGGGTAA

GCGCTTTAGA

TCGTCCAGCT

TAAGCAACTC

TTTATTGATC

GATGACAAGC

CGCCCTAGCG

CCGTGGGCTA

TGATGAAGTG

TCCTAATGGC

CCCCATTAAA

GCCTGTGTAT

GTATGGGAAC

AGATCATGTC

CGGGAAGAGC

AATTTTAGAC

AGAAAATAAA

CCAAGAGCAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 930 INFORMATION FOR SEQ ID NO:54: SEQUENCE CHARACTERISTICS: LENGTH: 999 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...999 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: GTGCTATATT TTTTAACCAG TTTATTTATT TGCTCTTTGA TTGTTTTGTG GTCTAAAAAA TCCATGCTCT TTGTGGATAA CGCTAATAAA ATCCAAGGCT TCCATCATGC AAGAACCCCA CGAGCCGGGG GGCTTGGGAT CTTTCTTTCT TTTGCGTTGG CTTGTTATCT TGAACCTTTT WO 98/18323 WO 9818323PCTIUS97/19575 129

GAGATGCCTT

TTTTTAGAAG

GGGGTCGTTT

AGCTTGCCTT

GCTATTAATA

TTAGTCATTC

GGGTTTATGG

TTTTTGGGTT

GTGTTTTTTG

AGGCGCAAAA

TTATTTAAAT

CTTATTCTAT

GCGCTCATTG

AATAGGCAAG

TTAAGGGGCC

ACATTAACCT

GCATCATTTC

ATTTCATCGC

TCATTGACGG

ATTATATAGA

TGTTAAATTT

TGGTGTGCGG

GGCTCAATTT

TAAAACGCCA

TCTTGCAACA

GCAACCTGCC

TGATTAGCCT

TTTGCGCTTT

TTTTGTTTTC

TTCATTAAGC

ATCAACGCCT

TTTTTT.ATTC

GTTTAACGGG

CCCTAGCAGT

CCCTTCAGGA

GATTTCTCTC

AATGCTTTAT

GAAAGCCACC

ACGCTCTTTC

TTTTATTTTA

AGTCTTTATC

AGAAAAGCGG

TTAGGGCTAT

CCCAAAATAC

TTAGTGGTGA

GCTATTTTTA

CTTGCATCTG

TTGTCTTGTT

AAGATTTTTT

TTGCATTTGA

CCGGTCATAG

ATGCCGGATA

AATTACCCTA

ATAAGCGTTT

GCATGCTATT

GCGTTTTA.A

CGCTAGTGTT

GCCTTATTTT

GCGATTTTTC

TGCTGGTGGG

GGATTTGCGC

TGCTCGCTTA

TAGGCGATGG

GTTTGGAGCA

AGGTGCTTTT

ATTTGCATTT

ACCCTTTATG

TGTTTCGCTT

TAATAGGCTA

TTTGAGCGGT

GCAAGCTGTA

GCCCCTTTTT

TATCAGTAAC

GATCGCGCTT

CATGGTGCTT

GGGGGCGTAT

AAAAATCAGC

TAGTATCCTT

GCACACCCTT

CGCGTTTATC

GGACGCTTAT

TGCTTATTTG

INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 816 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .816 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAACATAT

TTAGACGCCA

GTGGGCGCTA

GAGAAAGGGA

CTCAATGACG

AATTTGGACA

TTTTATTCTC

CCAAATGATC

GCTCTCAAAG

AACATCAAAA

GGGGCTATCA

GAAGATAAGG

GAAGCGATAA

GATACCTATA

TCAAGCGTAT

AACACCACAAL

ACCCTGTGCC

TCAAATTAGT

GCTCTTTAGA

GA.AAAATGCA

AAAAAATCAC

CGGCCAATCA

ACCCAAGCAA

TCAAACCCCT

TAACAGGGAA

ACTCGCCTTA

AAGCGTTGAT

AGGGGGCGAT

TATTTGCGTA

AGAAAAAAAA

GCATGCGCAA

GATCGTGTCT

CGCGAATTAC

CCTTGTTGGT

AGACATTAA.A

AGGCAGdGCG

TCTATACGCT

AGAAGCTGCG

TTATGCCTTG

TGCTAATCTT

TGAAGCCTTA

TATCCCGGCT

ACCGCTATTG

GAAGACCACA

ATCTTGCAAT

TTTACGGATT

TTCCAGCACC

TTGGCCAATA

AACCTTAAAA

TTGATTTTAC

ACGGAGTTTG

TTATTGCCTA

CAAGCAAAAC

GTAGCCTCTC

CAGAGCGAAA

TTTTAA

TTTTAGGTTT

AAATCACTCG

CAGTTGTGGA

ATGTGTTGCC

GCCCTTATTT

TCCATGTGGA

AAGGCTCAGT

TCCATAAACA

ATATTGTCAA

AGGTTTTAGG

TCACCGGAGC

GTGAGGATAA

AGACCAGGAA

TTTTAACCTT

TGAGCTTAAA

TGATTTGAAA

TAATTTAGCG

GGATCGGTTT

GCCTTTAAGA

GATTGCTGTG

AGGCCTTATC

AAATCCTTAC

GGATGTGGAT

CTTATTTTCA

TGCGCAAGAT

ATTCATTTTG

INFORMATION FOR SEQ ID NO:56: WO 98/18323 PCT/US97/19575 130i) SEQUENCE CHARACTERISTICS: LENGTH: 951 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .951 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:

ATGCAAGAAT

TTAAAGCTCA

GAAGCGATCA

GCTAAAGAAA

ATGCCTTTGT

TTAGAAGACG

CGCCCCAATG

CTGGCTCAAG

GAAATCGCTC

TCACGATTTG

ATCATGAACG

ACCCTTTTTG

GCGCTGTGTT

CTTGACCCAA

AAAGAATTAA

GGCTTGATAG

TCAGTTTGTG

TCAATAAGGG

CAAAAAGCGC

TTTATGAAAC

ATGAAAAAGA

ATGCGATTAA

TGATGATTAA

CCTCTATCCC

AAATCTTAGC

ACAAAGAAAT

CTACCGAGTG

CATCCACCGG

TTAAAAACTC

ACACCGAGTG

AAACGCACAA

CGTTCAAACA

GTGCGATTTT ATAGAAAGGG GGCTATTTGC GGGGCGACGA GTTTTATCAA GATGAAATCG TCTGGCACTA AAGGATATTT CCCTAACAAC GGCTACATCA AAGCATTGAT GAAGCCAAGC AGTCCCGGCG AGTGAAAGCG CATTAATGTA ACTTTAGTCT CAAAGAAGCA CGAAAAAGAG AGACCCACTA GTGCCACAAA TTATTATCAA ATCAACCAGC CGTTAAATCT AATTCTTTAG TATCAACACA GCCCCCCTAG TCAAACCCCT TTAAAAATCA TATTGATTTA GAAAACACCG

ATCCTTTGAA'AAGCTTTTAA

ATTTTTTAGA

GTAACCCTAG

CTAAACTCAA

TACAAGCCTC

GCCTAGAAAT

GGTTATTCAA

CTTTTGAAGT

TTTCGCCTAA

CGGTCATTAG

ATTTGCAAGC

ATGCTAATAA

CTAAAGATTA

ACGCCCTAAA

CAGAAATTGA

CCCAAAAACT

GCAGTTTTTG

AAACGATTTT

TTTGTTTTGC

AGGCAAAAAA

TAGCGCGTTA

TGACCCCTTT

AACATTAAAC

CATTAGCGCT

AATTGCCGGT

CGTGTTTGTC

TCAAAGTGGG

GCTAATAAGC

CTACATTAAA

CGCTTATTTG

AGCGTTCAAA

CCTTAAAGAA

A

120 180 240 300 360 420 480 540 600 660 720 780 840 900 951 INFORMATION FOR SEQ ID NO:57: SEQUENCE CHARACTERISTICS: LENGTH: 783 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 WO 9818323PCT/US97/19575 131 (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 783 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:

ATGAAAACAA

GTGGTGGCTT

AAATTGAATT

TTAAGGCCAG

AATCAAACCA

GTGGATAGCA

GTCGCTATGA

TCAGAACCCG

GCTGGGTTTG

ACGATGGATT

CATAGCGGAG

AAGAGCGCTT

CAAAGGAATT

TAA

ATGGTCATTT

TATTAGTGGG

ACCATCCAGC

CTTTCCAA.TA

CGCTTAAAGT

GCGATAAAGA

ATGGCGAAAT

GGTTATTATT

TCAAGGTTAC

TGAGCGAGTT

GGTTAGTTAG

TGAATAAGAT

TAGAATCTTA

TAAGGATTTT

GTGTAGCCCG

TAGCGAGAAA

CAGCGATAAT

TGAAGAGATC

CGATTTTTCT

TGTTTTACGC

CTCCACTGGT

CATACTAGAG

GGACATCCAA

CACTATGGTT

TTTTGCAAGT

TCAAAAAGAC

GCATGGAAAA

CATATTATTG

GTTCAAGCGT

ATTGCTAAAG

TTGCAAAATc

TTTGCGCAAA

CCCGATCCTA

TTGGATAAAA

CCTATGAGTG

GAAAAATTCT

AAGGGGACGG

ATCATGCAAG

GCCAAGGAAT

AATGCTTTTT

AAACCAATGA

TAGATGAAAA

AGTATGAAAA

AGGGCTATAA

AAAAAGAAGG

AAAGGACCAT

TGGAAAGGGT

GGGAATCTTT

TAAAAACCAC

ATAATTCTAA

AAATGGATAA

TAAAAAACAA

AGGCGCGAGC

AGTTGCTTTG

GATTTTACTT

CAAATTCAAG

GGTTATTAAT

GTATTTGGCT

ACAGAAAAAA

TTTAATCCCG

GGATTCTTTT

CCATTCAAGC

TGACGCAATT

GAAACTCACT

GAGAAACCGA

INFORMATION FOR SEQ, ID NO:58: SEQUENCE CHARACTERISTICS: LENGTH: 4149 base pairs TYPE: nucleic acid STP.ANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .4149 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:

TTGAATTTTA

TTAACTAAGG

AATTTATCTG

AACGCTCAAA

TATGGCATGA

TTTATAAACC

ACCATAGAAG

GAGCTTTATA

GACAATCAAG

GGCTCTCAAA

TTGAATATCT

ATAACCTTAC

CTTTAATGA.A

ACATCAATAT

AAGGGATTAC

AAATCCAAAA

CTCTCAATTC

TTTTAAATAA.

ATTACCAAGA

CAGGCACTTA

CGCCTCAAAC

ACAATAAGGG

GGCTAATGGG

TGTCAGCGGG

CTTTGACAAC

TGGCATTAGT

CGCTACCTAT

TTCTCAAATC

CCCTAACTCG

TTCTAAGCAA

TTACTTGACA

CCCAGGCACT

TTTTTCTAGC

GCGTTAAATT

CAGTTTGTTT

ATCACAAAAT

GGGGCTAATG

AGCGATAATA

ATTCAAGAGA

GCTTCCAACA

AATCCTAC CG

AGCAACATTA

TATAGCCCAT

GAGAATTTA

TTAATGGTTA

TAGGGAATAA

CTGTAACTTA

GCTATGAAAA

ACAACATCCA

GCATTAAAAA

CTATTTTTAA

GCTATAGCTA

A.AGGTCTTTT

TTAACCAGCC

AAACGCTTTT

TGCGCCCTCT

TGGGGATATT

CAACATCTTA

AATCCTTTTT

AACTTGGTCG

TGGGGATCTA

TATCGCTCCT

TGATTATAGC

CACCCCTAAA

TTTGAATAGT

AGGGATCCTT

120 180 240 300 360 420 480 540 600 660 WO 98/18323 WO 9818323PCTJUS97/19575 132

TCTCAAAATT

AACATTAATG

GCGCTCCTAG

AATCTCGTTA

GGGGGCAATG

AACACTTACT

GATTTTAAAG

AGCGGAGGGA

AACATAGAAG

AAAATCTTTA

AAGCAAGCCG

TTACCCGCTA

GATTTATTGA

AGCATTTTTG

TTAAAAAGCA

TCTGAATTAA

CTGCAAAAAG

GTTGTCAAAA

CAAGGCGGGT

CAAAACGCGC

TTTTGGCAAA

TCTTTTAGTA

AATGGCGATA

GGTGTTTCTA

GGTTTGAATA

ACAACCAAAA

GTGCACGCTA

TCTCAAGTAA

CAAGCTAATA

ATTGATGGTA

AATGTCATGG

AGTCATGCTA

ATCCAATTCA

GCCATTTATT

AAGCTTTATG

ACCTATAACG

TCTCAAAATC

AATGATCCTA

GGCGTTCAAA

AATAAAATCT

TCCACAAAAG

AACCCTAATT

ATGAGTCGTT

CGCTTAGAAG

ATTTTAAAAT

GGGGCTAGTT

AGGTTTATTA

GCAAACATCA

ATCAAAAGAA

ATCAACTCCT

ACGACTGACG

TTTAA.ACCCC

ATGGATGATC

CTAACGATCA

GTGATTGCGG

CCGCCACCTT

AAGTGTTGCA

AAACGATCAA

TAGGCGCTAC

GCTATAGCAG

TGGGGCAATT

CTAAAAGCAT

GCGCGGATGT

CTCAAGCCAC

ATCAGGGGAA

GCGGTTTAGG

GCTTGCAAGA

ATAATAGTGG

GCAATTTTGT

TGCTAGACGA

GCTCTATTTT

ACATTGGTGT

AGCTAGAAAG

TGAGCGGCGT

TCAAAGAAAA

AAGGGTATTT

ACGCTACTGG

ATACGATTGA

ATATCAATAT

ATGTGAGCGT

ACAGCTCTCC

ATAATTTCAC

CAAATAATAG

ATTTAACGAT

ATTTCACCTT

GGAATTTTAA

TTATCAATAC

ACGCTTCTTC

ACGGGTATAA

CGCTCATTGA

GGCAAGCCGT

AATACATTTA

TCAATAACCC

GCGTGGATAG

TTGAAACTAA

ATTTAACCAC

TTAAAAATGA

TAGCCAAGCT

CCCTTAAAAA

ACTCTCAAAG

TCATTAGTGG

AGGGCGTGAT

CTCAATCAGG

GCGAGCTAAC

ATGACCCCCT

CTAAAATCAA

AAGTAGGCTT

CTATTTACAA

ATTTTGCCCT

ATGTGGGCAG

AAAAGAAATG

ACTCTTAGAT

CCATTTGACT

CCAAGATAAT

CCCTTGCGCG

ATTAGGCTCA

TTATATTACC

AACCTTTCAA

AGACAATATC

TTTAGCGAAT

GAACTTTATA

TGAAACCTTA

AGTCATGAAT

TACCCCATCC

TAAAGGGCTT

AGGCGTGATT

GGTAGCGAAC

TCAAGGCTTG

TTATAATCAA

CGATTTAGGC

TAACTTTTTA

GGGTAGTTTG

CTTTAGCAAG

CACCACCCTA

TCAAAAAGGA

TGCAAACTCT

TTITCTTAGGC

CGTTATAGGC

CACCAACGCT

AAACCAACAA

TAGCTATGGC

TCAAGGCACA

AAAAGAAGTG

CAACCAAATC

TATTAATGGC

GAGCGTTAAA

CACTTCCATT

ACAAGCCCCC

CATCGATCAA

AGGAAGCCCT

GATCGCTGGA

CGCCACTAAT

CTCTGACACT

CAAGCGATTC

GAATAGAGTT

AGGTACtGGA

TGTGGGAGGT

CTCTAGCAAT

CATGAGCTTG

ACTCTCAATC

TTATGGCTAT

AAGCTATTAT

CCAATTCAGA

AGAAAGTCGG

AGACTTATTC

ATTGAATCCA

AAGATTAAAA

GACAACATCA

GTTACAAACT

CTAGATAGCG

ACTTCCCCTT

GGGACAATTG

AGCGCTAATA

TTTAATCTTT

GTTCTTAGTC

GAAAACGCTC

GGCCAACTTA

GAAATCCAAA

ATCATAGAAA

TTGAATTTTA

TTA-AAGGATA

GACTTGTTGA

GTGAGTAATA

GGTTTAGGGA

ACTCTTTTAT

AGCAATGGCT

AATTTTGTCG

TATCAAGGCG

AACGCCACTA

GAAATTTGTA

AGCGTAACCC

ACAATCATCT

ACGCTCAATC

TTTAACAACG

GCGACTTTAA

GATTTGGTGT

GCGACGATCA

GGTACTTACA

ACAGGAGGCA

AAGCACATGG

GATGGCGGTT

CTTTATAATA

ACTTTAAAAC

GCTGGGGGAA

TTATTCGCTC

GATATTGCTA

ATTTTACAGA

TCAACTTTCG

GCTGATGCGA

AAAAATAATG

ACTTTATATG

TATGCCGCTT

GTCAATGTGG

AATGAGACTT

ATCAATCAGT

GATTTCATGT

TACATTGGTT

GCCAATGCTG

CATTATTTCA

ATTAATTCTA

ACCAACTAGA

TCACCCAAGC

ATCAAACCTT

CTACTAGCTC

CCACTTGTTC

ATTTAGGCTA

GAAGTAGTAA

ACTTAGTGTT

TGGGTCAAGA

AAATGGCTAT

TAAGCCCTTT

TAGGTCAAAA

ACATTATCAG

ACTACCTTGC

TCGGTGGGTA

TTACTAACCC

ACGAGTTTTT

TCATCAATAA

GCGTGTTGCC

CGCCTAGAGG

ATGTTTTTGT

CCAACAAGTC

CATTGATTTT

ATGGCTTAAG

TCAATTTAGC

CCACTAATGA

CTAATGGGGC

TCAATGAAAA

CCTCTAACTC

GCACTAACGC

TTAACCTCAG

TGGCCAATAA

CGCTGATTGA

GTAGCCTGGA

TGATGACTGA

TAGTTGTAGG

AAGTGAAAAT

AATATATCGC

ATCAAGCGAT

CCTATTATCT

ACACTTTAGA

TCAACACCTA

CCCGTTCTGA

TCCCTAACGC

TGTGGGCGAC

GTATCAATGT

ATGGGTATAG

GCGTTTATAG

GGGGATACAA

CTTACAGATA

TTAAAGATAA

TGTCTGGTTT

AC CCTAATAA

ATAAAAACTC

TGGGGGATAA

CAATATCACT

GCAAAAGCAA

TAATAACGGG

TATATGGTTT

TTCTTTTAGA

CATTAACGCT

CGCTTTTGAA

GAATAAAGCT

AGGGATTGAT

GGAAAAAATC

GAGTAAGGAA

TAACTTAGAT

TCAAAAACTA

TAAGCAGTCT

TATAGACGCT

CCCTACAAGC

AGGACAAGAT

TGTTATTTCT

GCCCTCTTTA

CTTGCATGAT

CAATAACAGC

TATTATCTTT

TGCTTCTAAT

CCTTAATGCG

CAATTGCCCT

GTCTTTAAGC

TATTGATTTG

TGCGACCTTG

TACGGCTAAT

TAGTGGTTTG

TCATTCAGTT

TAACCCTTTG

TAGCGCTAAA

TAATTACCTT

CAACGGCTTA

CTTTAAGGAC

CGCTGTTTCT

TCAALATTCAG

TAATTGGCTC

AGAGAGCCAC

AGTCATCGCT

CACGCAGCAA

TTTCTTAGAA

TATGGATGTG

AGGAGTTGGA

AGGGTATGAT

CGGGTTCCAT

CCGAGCGTTT

TAAAACTTTC

CGACACTTGG

AAGCGTTATT

AAGGGGCATT

AAAATCCGTT

TTATTATTTT

AATGGTGCGT

720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 WO 98/18323 WO 9818323PCTIUS97/19575 133 TTCATCGGTA ATAACACCCT AAGCTATAGA GATGGTGGCA GATACAACAC TTTTGCTAGC ATTATCACAG GCGGGGAGAT AAGATTGTTC AAAACCTTTT ATGTGAATGC GGGCATAGGG GCTAGGTTTG GGCTTGATTA TAAAGATATT AATATTACCG GAAATATTGG TATGCGCTAT

GCTTTTTAA

INFORMATION FOR SEQ ID NO:59: SEQUENCE CHARACTERISTICS: LENGTH: 789 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc feature LOCATION .789 (xi) SEQUENCE DESCRIPTION: SEQ ID NO*:59: 4020 4080 4140 4149

ATGAAAAAAA

GAAGTGAGCG

ATGAAAATCA

GCAAGAGAGG

TATTCTTTAG

CTAGAAAATC

AAAAACCCTG

GATGAAGCAA

TATATGAAAA

GCGTTCAAGT

AAAGAGGGCG

CTCTCTTCAT

TTGGTTTGAG

CTGAAGAGAT

ACCACACGAA

ATTTAGAGGT

GGGGCGTGGC

AAAACGCTAG

AAGAATTCGC

GAATCAAAAA

CGATAGGGAT

TTAAAGATAA

TTAAATACTT

TCCAACAACA

CTTGTGTTTG

TGCGGATATT

GGGGTTTTGC

GCCACTACTC

GATGGACGAT

TTGGACAATG

CCAATTTTTT

GCTTTAC!GAA.

TAGCTCAAGC

GAAAGAAAAA

AAATCCTCAA

CCTTAAAAAT

CACCAACGAC

GTTTTGAGTT

TTCTACAAAC

GCTAAAGGCG

AATGAAAAAG

AAAAGCAAGG

GTGATGCTCA

GAAATGAGAC

GAAGTCCCCT

GTGGCTAATA

TTATTGCCTG,

GAATTAAAGC

AAACCCATAG,

ACGACCGCGC

TGGGTTTTTT

TCAACGCCAA

TGTTCCTCCC

AAATCCCTGC

TTAGGGGAAT

ATACAGAAAT

TTCCTAAAAA

CTTATAGGAA

CGCCTTATTA

CGAGGTGGAA

AAAAAGATTC

AATACCAAAT

TTTGGAAAGG

AAAAGCCCAT

AGAGCCTAAA

TAACCCGCAA

GTCTGTAAGG

GGCGTTAAAA

CAATTTTGCC

TGGCAAGGTA

TTTTGCCGC

TAGCGTGCAT

ATTTGTGCCT

AAATTATCTG

GTATTTGGTG

CAGCATAAGG

TTTGCGAATC AAAATGATGC

AATTATTAG

INFORMATION FOR SEQ ID Ci) SEQUENCE CHARACTERIS-TICS: CA) LENGTH: 741 base pairs TYPE: nucleic acid CC) STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/18323 WO 9818323PCTIUS97/1 9575 134- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .741 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAAACAAT

ATCTTAAAGC

TATGCGGATG

GTGCATCGTC

TTTACAGGAA

CACTCTCAAA

TTAAGCGGTC

TTAGGCAGTA

TATCCTAATG

GTAGAAGTGG

AACTTGAACG

GTGAATGTAG

TACTTGCAGT

TTAAAAAGAA

GTCCTTTATG

GAACAGACAT

CATGGTATGC

ACCAACTCAT

ACAACCAAGA

TGTATAACTA

ACGCTACTTT

GGCATACTGA

GCAATCGTGT

CTAATAAGGT

GCAATGCTAA

TCTTTAGCTA

ACCAAAAAAG

GCTTATGCCT

TTTGGGGCTT

TATATGGAGT

CACAAAAACT

CATCACAGCC

CACCGGAGGG

TAATCTAGGT

TGTTACTTTT

GGGATCGGGA

TACTATCAAT

CAGCGTTATT

ATAAAACGAT

TTACTGATTG

AGTTGGGGGG

TGCGATAAAT

TGGGCAGGGG

AATTTAAAAA

GAATATAATG

GCGAGTAGTG,

AGCGCTGGGA

GCTGGCACGC

TCCAATATCA

ACCATTAATT

CGCATCAAAA

GCGGGTTTGC

AAAAAAG CCA

GGGAGGAAAA

GTAATGCGGC

ATGATAACGG

GGGGGAATTT

GGAATAGCTT

CTATCAATGT

ACACCGGCAC

GCGCGTATA.A

CGGTTTCTTT

TCAAAAAACA

TAGTGGGGTG

AAAGGTATGC

AACACAACAA

TAACTACTAC

CACTTATTTT

AGACATTGAA

CACTTCTTGG

GAATAACAGC

AGCCACTTTA

AACTTCGCAA

AAATGGGGAA

120 180 240 300 360 420 480 540 600 660 720 741 INFORMATION FOR SEQ ID NO:61: SEQUENCE CHARACTERISTICS: LENGTH: 738 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .738 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:

ATGATAAAAA

GCCAAAGAAT

ATCAGAGCCT

AAGCTCGTTA

ACTTTTGATT

GATAAATTTG

TACGCTAATT

AGACCCTTGC

GCGTTTCGCC

TGCAATTACA.

AAGACAAAAA

ATGCGGGCTA

AAAAAGAAGG

CTAAGGGCGT

ATCGGTTTTA

CATAACAAGA

AAGTTACAAA

GCCAGCCGTC

TTTAGTCAAA

CTCTCTTACG

TAAGATTTTT

TTAGGATTGA

AGCGTTAAGT

ATGGCGAA.A.A

ATCTTGGATT

AACTGCATTA

CTCATTCCTG

TACATTTCTA

GTTTGATGAG

ATCATCAGCA

TGGCGCTAGA

TAGATGAAAC

AATACACCCC

GAGCGCTAGA

ACCGCACCCA

TGTGTTAAAT

AAGTGCTGAG

CAATAACCTT

CGTTTTGAAC

AGAAACTTGG

CTTTTTAGAA

AAAAAATAAG

WO 98/18323 WO 9818323PCTIUS97/1 9575 135

GCATTCACTT

TTGTTAAAGG

GCGATTGTTT

GCTAAAAACA

GAATGGATCA

TGGCAAAATA

TAAAAACGCT

AAAAAGGCAA

TACAAGTGGG

GCCAAGAACA

TTTTACCCAA

AAAAATAA

CAAAAGCTTT

GCCTAAAGCC

CGACACTTTG

ACAAGCCAAA

CTCTCTTTAT

AAGCTCCCCC

GTTAGGCGGG

CATGATTTTG

GTCTTGCAAA

GGCACATGGG

AAGTGAGTGA

AGTTAGTCGC

ACGCCATTTT

ACGCTCAAAA

AAGATGGGCC

AGAATCCGTT

TAAGGATTAT

TGCTAAAGAC

ATTCGGCACA

TATAAAAGCA

INFORMATION FOR SEQ ID NO:62: SEQUENCE CHARACTERISTICS: LENGTH: 867 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .867 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:

TTGTGGTGTT

TGGTGTTGTT

TCAGACGCTA

ATCCTTGCGG

CTATTGAATT

GAAGCGTTAT

GATTATGTGA

GACAGCGTGA

AAGATTAAAA

GCGACTTCAG

TATGTCGGCG

AGAACTACCG

TTGCAACCCT

CGTTACAAAA

GTTTTTATTC

TAAAAACCCC

TTAAAATGAT

AAGAAATCGC

ATAAAGTGAG

ATGACGTGTA

TAGA.AGGCAA

AATTGAGTTT

GCGGGATTTG

ACATGAGCGC

GCTCATTTAA

ATATTCCTGT

GGTTTTTATA

TTTATTTAGC

GGGGTTTTGG

AATGCGCGCT

TATCATAGGG

TCGTTGGTTG

TATGCAACGA

CGCCAAAGAC

TATTCTAGCG

TATTAAGGTT

GAACGAAAAA

GGTGAGCGCG

TTCAGGGTGC

CATGCAAAAA

ATTGTATTTG

CCCTGAGTTT

CCCCAAAAAC

CTTGAATTTT

ATTTTAG

CATGGCATGA

TATTTGGCGG

TTTGACAAAC

AATGTGATAA

GATAAGGTGC

TATAGGGGCG

TATGAGATCA

GATATTGCTA

AGCATTGACA

TCGCATTTGT

CCCTATATTT

GGCACTTCCA

TCATGGGATA

GAAGCGCGCT

AGAAAAAAGC

TCTTTTTTTT

A.AAACCATAA

CCGCCTCAGG

GTTATGACAC

AGGGCTTGCT

TTTTCCCCTT

GCGGGAAGGA

ACCCCATTTG

CAATGTGGAA

TCATGTCCAC

ACTTAGACGG

TGACCTTTAC

ACATCAACTC

AAAAGTCTTT

GTTGAGCGTA

GATTTTTGAA

GAATGCGATC

CAAGACTAAA

CGTTAAAACC

TTATGTCCAA

TCAA.AAATAT

GCATGTCAAT

TCCTAAGATT

GAGCAATAA-A

CTTTATTTAT

CCCACAAATC

TAAGACGCAG

120 180 240 300 360 420 480 540 600 660 72 0 780 840 867 INFORMATION FOR SEQ ID NO:63: SEQUENCE CHARACTERISTICS: LENGTH: 387 base pairs TYPE: nucleic acid STRANflEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE,: DNA (genomic) WO 98/18323 PCT/US97/19575 136- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .387 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:

TTGATGTTTA

AAGGATTTGG

ACGGACTCTA

CTTATTGTCA

GATAAGTTTA

TACCGCCTGG

GAATATTACC

AAAAAATGTG

ATTTCAAGCT

GTCTTTTAAG

ATAGGGGAAA

AAAAAGAAAA

ATTGCAAGCC

ATAAATTTTC

TTTGAGCCTG'

GGATTATCGC

TATCACTTCT

TTCATGCGAA

ACTCTTTGAT

TAACCAATTG

CAAATAG

CTAATGATAA

GCGACTGGGG

ATGAACGATG

GCGACTAAAA

CATGAATTAA

TTAGAAGTTA

GCGGTGTTTG

GGAAATTCAT

AACCGGTGGT

AAGTAGAACC

AATACTCGCA

AAATCATCAC

TGTGGGGGCA

GGGGAAAATG

GATTAAAAAC

CAAATTTGGC

ACAGATATTT

GGACAAGGGC

INFORMATION FOR SEQ ID NO:64: SEQUENCE CHARACTERISTICS: LENGTH: 510 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 510 (xi).SEQUENCE DESCRIPTION: SEQ ID NO:64: ATGCAAGCGT TAAAATCATT'GCTTGAAGTG ATTACAAAAC TCCAGAATCT AGGCGGCTAT

TTGATGCATA

TACGAAGCTG

AAATTTGAAA

GAAATGCAAG

TATTTAGTGG

GGGCTTTGGA

ACCACCCTAT

GCTTTCTGGG

TAGCTATTTT

AAGGGATCGC

AACCTGCATA

ATAACCCTAA

CTGAAGGTTT

TGCCTTTAAT

TCTTTTTTAT

GCTGGAAGGC

CATCATTTTT

CCCTTTTGTG

CAAACAACAC

AATCGTTGAA

AGGGATTACG

GGGCGTAGTT

TCACAACGCC

TAGTGGTTAA

ATTTGGATTG

GCCAACTCCC

AAAATGTCTG

AACAAAGAAT

ATCATGATCC

GGGGGCTTGC

AGAAGTGTTT

GAGGGCTTAA

CTTTCTTTTC

AATCCCAATC

GGCATAAAGA

TAGGCATTTT

TTGTCGCTGG

GTCAATCAGC

GTTTGTGCCT

TTTCATGTAT

CATGCAAGAA

AAACCGCACT

GGTGCTTTTG

AATGACGATC

ATTTCCCATG

120 180 240 300 360 420 480 510 WO 98/18323 137- INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1464 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM:-Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 1464 (xi) SEQUENCE DESCRIPTION: SEQ ID PCTIUS97/19575

ATGATTGAA.T

ATCGCTTTTA

GATAGCGCTG

CGCCGCCTTA

CAAATCAAAG

TTGAGGAATT

ATCAGAAAAA

ATCTTAAAAC

ATCCTTCAAA

CTATCGCTTT

GTTAAAATCT

TTTAAAAAGC

ACTGATTTGA

GAGGGGAAAT

CAAAAGGCGA

AACTACACCA

AAACTCACCG

ATCGTGGTGC

AGCGCTCTTA

AA-AGAAAAGC

GGCACTATCA

CGCCAGGAAA

GAGCAAAATT

AATAACACTA

AAGATAGTCA

GGATGCAAAA

TTGCCGCCGG

CCAAAGTGGG

AAGACGCCTA

CCATGCATTT

TCGCTTTAGA

CGAACGTTTT

AAAGCCATTA

AAATCAGCGC

GGGCAAAATT

CTCTCAATGA

CCACAAGCTT

AAGAGTTGGA

TACAGGATTT

ATGAAAAAGC

CGCAAGATTT

CTCTCAAGCC

AGCTTGTCTC

AAACCCGTCT

TTAAGGATTT

GTGAACTTAA

AAAAAGGGTT

TCAATCACCC

AAACGGATTT

AATACATTCA

TCATAGAAAG

AATGATAGGT

ACAGATTAAG

TGCTGAGTCT

AGAA.AAAAGC

TTTAGGGCTT

TCAAAAAGAT

CCGCCCCAAG

TCTATTCCCC

GCAAGACAAA

AGAAGAGATG

TAAAACACGC

GGAATACTAC

TAAAAGCGTT

CTTAAGGAGC

TGAAAAAAAC

CCTTGAAGTC

TCAAATTAAA

GACTCAAGAA

TAAAGGGAAA

CCAAGAAGAG

TGTAACCATA

CTTTAGtGCA.

TTTTGATAAA

ATAA

TATTTAGTGG

TGGGGGCAAT

ATTTCTCAAG

ATCCCTGATT

GCGCTAGATT

GGTGCTACCA

GGCGTTTTTG

CATTTTGAAG

AAAACCACCA.

TTAGACATTC

AAAAAATATT

TCTTTATATT

CATAAAAACA

CAAGAGCAAG

TATATCGCTC

AACTCCCCCT

CTAAAACCAG

GACGAATTGC

AAAACCCTTA

AGCGTGGGTT

AGCGCGAAGT

GGTAATAAAG

GAAGAAAACC

GCGTTGATAG

TTACGATATG

ACAGCTTTTC

AAGAATTAGC

TTAAAGAACT

CGCTCATCAA

AGCAAGAAGT

ATGAAGAATT

AAAGCGTTGA

CCCCTTTGGA

TTATCCTAAA

ATGAAAACCA

TTGACGCTAG

AGGTGTCTTA

TCAAGCATGA

TAAAAAAGGG

ATACTGCTGA

AGCCTTTTA.A

AAAATTTTGA

TGGCGTTGCA.

ATGTAAGCCC

TTATCAACAC

TGGTGCTTTA

AATACATGCA

AAGAATTGAA

GATAAGCACG

TTTAGATAGC

CCAAGAATAC

CACCGAAGAT

TCAAGCTTTA

GGCCAAAGAG

GTATAAAAAT

AAGGCTTTTA.

GCAATCCAGT

TCCTAATGAT

TAGAAAGGAT

TTTAGAAAAA

TTTGGACAAA

TTTAAACATG

GAACGCACAA

AATCACGCAA

AGATGGTTTT

TGAAGCCAAA

AACTTTAGCT

TAATTTTGGA

CCTTTTTAAC

TCAAATCACA

GCGTTTAGTC

AAAACGCTAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1464 INFORMATION FOR SEQ ID NO:66: SEQUENCE CHARACTERISTICS: LENGTH: 429 base pairs TYPE: nucleic acid STRANDEDNESS: double WO 98/18323 WO 9818323PCTIUS97/19575 138 TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: 0 ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .429 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:

ATGAAAACGA.

TTTAACGCTC

ATGGCGCTAA

GAAACCCTAG

AAGTTTGACG

ATGTGGGGCA

TCTTTCATGT

GGGTATTAA

ACTTTTATAA

CGCTTAACGC

ATAGCGTGGG

AGCAAAAAGT

ACATAAGTTT

TTCAAAATCT

ATGGCTATGC

AATTAAATTA

TGACCAAAAC

GCTTGTTTCT

GGCCATACTC

AGGGAGTTTC

TCTCATGAGC

GCCAACATAC

CTATTTGCTT

ACGGATATAA

AGAGATCAGC

AATGACTATA

CAACCTAATG

CAAATGATGA

TCAGATTCAT

GGTGTCTTAT

AAGATATTAG

TAAAAATAGA

ATGATAAGAA

ATAATCTAGG

GCAATTACGG

CGTTTTTACC

CATTGGCATG

TCCTGAAGAT

GATCCCTAAA

TGTTAA.TATC

TATCAATGCG

TCCAAACAAT

ACCGATCTTA

INFORMATION FOR SEQ ID NO:67: SEQUENCE CHARACTERISTICS: LENGTH: 627 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .627 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:

TTGATCAACA

AGTCTCGTTG

GCGCTAGAAA

AGTTTTAAAG

CCCGATATTA

ATAAAGGATT

ATAATAATAA

TTTTCAGTTC

AAGAAAAAAA

CGACTATCAA

TCAAAGATGA

TGAAGCATTA

CAATAAAAAA

GTATGGGTCA

CACTCCCAAT

AAATTTGAAA

AGTTTTTGAC

CGATCCAGTT

CTGAGAGGCT

GCAAATGACG

GGGCTTGTTT

GACAAGAAAG

TTCGTGATTG

ATTGAAAAAA

TTTTTTTGAA

ATAAAGAAGC

ATACGAATTT

TAACTTTCAA

TCAATAGAGT

TCTTTGATGA

AGTTCTCTTA

CAAAAAAGAA

AGATTTTGAT

AGAAGTCAAT

CCTTAAAAAA

AAAGGGTAAA

WO 98/18323 WO 9818323PCTIUS97/19575 139- GAAATGGGAT TGAATGTAGA ATTACAGATC AATCCTGAAG TGAAAGACTT TTTTACTTTC AAAAGCATCA GCACGACCAA CAAACAACGC TGCTTTCTAT CATTGCACGG AGAAACAAGA.

GAAATTTTAT GCGATGATAA GCTATATAAT GTTTTATTGG CCGTATTCAA TTCTTATGAT CCTAATGATC TTTTGAAACA CATTAGCACC ATAGAGTCTC TCAAAAAAAT CTTTTATACG ATTACATGTG AAGCGGTATA TCTATAA 420 480 540 600 627 INFORMATION FOR SEQ ID NO:68-.

SEQUENCE CHARACTERISTICS: LENGTH: 738 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .738 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:

ATGGCAGGCA

TCAATCATCT

ATGACAGCAG

ATGACCCAAT

CAACAATACA

ATCTTAAATA

CAAATTAGTG

AATCCTAGCG

ACGGTTGAAA

CTAGCTCTAC

GATTCCCTTG

AGTTGCATGC

ACCAGCGGTT

CACAAGCTAT

CAAGCACAAG

CGATTATTCC

ACAATCAAAG

ACCAATTGTA

TCAGCAAATT

CTGTCAATAG

CTATTGAAGC

TGATGAGCGG

AAGAGCAACT

ATAGCTGTAC

AAATTTCTAT

GCCACTAA

ATATGAATCA

TGGTGTCGCA

TATTGTTGTG

CATCGCTGAA

TCAAGGTTTT

AACAGGGGAA

TCAGATTGCA

TTATGCGACG

TATATTAGGC

GCGTTCTCAA

CGCTTTAGGC

GACTCCTATG

TCTTCTGCAG

GGGCCATTTG

GGATTTACTA

GCTGTAAGCG

AACGATCAAA

TTTAACGCGC

AGCATTTTAG

AATCAAATCG,

AATATTACAA

GCAAGCAACA

GCACTTGTTG

AGTGTTTCTA

GATTCTTATC

CAGGAATAGT

ATCCGCAAAT

TGCCTATGAA

GCATGGCTGT

AAGGCAACAC

CGAGTAACAC

CTGTTCCTAG

GCGCAGCACC

GCTCAATGAA

GCTCATCAAA

TGCCCACTGT

GCAAGTCTCC

AGCGGGCGCT

GACCGCTATC

AGCCGCTAAC

GGGGAACAAT

GCAAAGCGCG

TACCCCTAAA

CGTGCCAACA

AAAATACGCC

TGATACAGCC

AGTGTTTTTC

TATGCCAAAT

120 180 240 300 360 420 480 540 600 660 720 738 INFORMATION FOR SEQ ID NO:69: SEQUENCE CHARACTERISTICS: LENGTH: 1104 base pairs TYPE: nucleic acid STRANUEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/18323 WO 9818323PCT/US97/19575 140 (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURlE: NAME/KEY: misc feature LOCATION 1 .1104 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: ATGATTAAAA GCGTAGAGAT TTTAAACTCA TCAACTTTTT

GCTCTTTATA

GAACATGCCG

ACCTTTTTTT

GCTACTATCC

TTGAATAGCG

CTCCAATTTT

CAAAACCTAG

GCGATGTTTA

CAATTAGCAA

TTAAATGCTA

CTAGAAGAAA

ATTATGGTGA

AGCGGTTTGC

AAATTACAGA

AACACGATAT

AAAGAAAGCG

AGGGGTATGG

CCAACACAGG

TGAATATTAG

ATCAAGGAAA

CTCTTACTAT

ATGATGCTCA

CCTACAATCC

GTTTAATCCA

TTCCTATAGA

GCAAAGAAAA

ATACAATAAG

GTCCCAAAAG

GCATTCTTAT

ACCATACAAA

TTCAAATTTT

CCGATAATGA

CTTCTGGCTT

AGGTTAGAGG

TGAAAATTAC

TACCGGTCAA

CCTTTGTGAT

TGAATTCAGA

CACCGCTAAT

CCAATACCCC

TATGACAAAC

ATCCCTTTCC

TTCTAATTTA

ATTATCTATT

AGAATTGATT

AAAGTCTGTC

GCTTTTAAAT

AGACAATCGT

AATGCAAGAG

TGCCACCACG

AACGGGAGTT

TATCAGACAC

CTGA

AAAAATTTTG

AACGATGCGG

CCTACTGCCA

AAAATCAAAC

CCCATTAGTA

ACACAAACCA

CTTATAAACA

CCCATGACAA

GATAAAATCG

GTTAATTCTC

GAAATCCTAC

TATATCCAALA

TTGTTTGGTT

GTCAAGTATC

TTTTTAAAAG

CACAATAAGG

TTTAAAGACA

AGCTATTCTA

AGCACCTTAA

GTAAAACCAA

ATCAAGTCAG

TCGATGCCGA

TCCGCACTGA

GTTACAGCAA

CAACAATAAC

TGACTTATGA

CTCAAACCTA

TTAAAGCATT

AATGTTTCAA

TCAAAGATGA

GGGGTTTTAT

TTTTTATTGA

CTCTGTTTAA

AATTTTTATT

TAGCCTTGTT

TGCTAGAAAA

AATGGAAAAT

TCTTTTAGAA

TCTTCCTCCT

CAACCTAAAA

ATTTGAACAT

AGACATCAAT

GAAGCCACAG

ATTTGAAAGG

TAAAGAAAAT

GGAAAA~TTTA

CCCTAATATT

AAACACACCG

CAAATTCTTT

TGAAATAGAA

GTTAGCTCAA

AAACGCCATC

TGAGCTTGAA

AGCGCTTTAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1104 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1230 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .1230 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGTCCTTGA TTAGAGTGAA TGGGGAAGCT TTTAAACTCT CTTTGGAAAG TTTAGAAGAA WO 98/18323 WO 9818323PCTIUS97/19575 141

GATCCTTTTG

GTTGTTTTAT

CTACGCTCTC

GACTTTAAGG

TACCCCAAAA

TTGAAAGTAA

ATGGAAGCGC

CCTTACTTGC

ATCAAACTCA

CAAGGGGGTT

TATATTGAAG

ACGCCTTTTT

TTCATTAAAG

AAGGCTCATA

ATTAAAGGGG

TCTTCTAAAG

CTTGAAATGG

ATTTTAGAGA

ACTACAATGG

GTGAGCATGC

AAACTAAAGA

TGGCCGCTGG

ACCACACCCC

AAGTCATTCT

TCAAGCTTGT

TTGATAGCAC

TTAAAAGCTT

CTTGCTATGA

TTCAAACCCC

TTAAAGATGA

GCAGTAAGGA

TTAACCCAGC

ATAAGCCTAT

GCGATGGCGA

GGGATATTGG

AGCTTTTAAA

GAGCGACCAT

ATTTGAGCCA

AAAAAATGGG

GTTATAAACA

AACGCTAGAA

GGAGTCTAAG

CTTATGGCTC

AGTTGTAAGC

AAAAGGCGGG

TTACACGATC

GTTTTTAACC

CACAGCGATC

GCAATTAAGC

AAGCAGCGCG

TTTGCACAAA~

AAAGGACACT

GGTTTTAGGG

TGCTTTATTG

CGAATGGTTC

AATCGTGTTG

CTTTAGCGAA.

ACTTTTGGGT

GTTCATTGGC

AAAACTTTAA

ACGCTAGAAA CGCTTATCAA

CGTTTTTCTC

AGCGTGTATG

GAATTGGATT

GCATCAAGGC

ACCAGCGATG

CTCCAACAAA

TATTATAACG

CACACCAAAA

ATTTTACAAG

CTCACCACAA

TTTATAGGCA

GGGGTTGTTT

CATGCGGTTA

CCTGATAATG

GATTTTTCTC

ATCCCTAAAA

TTAGAAAAAT

AAACAAGAAG

GTGCGATTAA

AAAGCTTTAA

ATGTTTATAT

AAGAATCCGT

TGGCTAGGGG

CGAGCCATTA

AGGCTTTAGA

CGCTCCAATC

CTTTCCCTAA

GCGGCGATTT

TGGGTTTTGA

TGGATTGCGA

TTGATGCGAT

ACCCCAAATA

AAAGCATTGG

TCACTCCTTA

CTCAAATCAG

GGCTGTTAGT

ACAAACGAGC

AAAGCAGTGG

AGAAGCCCTA

CCAACGCCAT

GCGTAACGCT

TTTAGCGAAT

TTGCATCGCC

TAGAGAAGCG

AG CC CTAAAC

CTCTGTGAGC

AAAGTTTTTT

TACGCATGCG

GTTTGGGTTA

TTTAGGAGCG

CAAA.AACGCC

GTTTGAATTG

CAAACCGGCG

CTTGAAAGCC

CCAAGCGCAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1230 INFORMATION FOR SEQ, ID NO:71: SEQUENCE CHARACTERISTICS: LENGTH: 813 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 813 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:

ATGAAAAAGT

GAAGGTGATG

AATATTTATA

GCTAATAAGC

GCTTTGAATG

GATATGACAA

GATTTAGGTA

GTGGGGAGCG

GGTGGGGTCG

CAAATCATTG

CCTTATAGCA

TTGTAGCTTT

GTGTTTATAT

ATACAGGGGA

ATAATCCAGG

GTTTTGGGTT

GCAAGTGGTT

AACAAGTTTA

ATTTGTTAGC

CTATCGGCGG

AAGCCAAAGG

CCAACACTTC

AGGGCTTCT.A

AGGGACTAAT

TTGCACAGGG

AGGCACCAAT

GAATGTGGGT

TGGTTTTAGA

TGCACCTAAT

TGATATTATT

TAACACTTGG

TCCTGATGTT

AACCGTCGCT

TCCGCGGTTT

TATCAGCTTG

AGTGTTGTAG

ATCAATTGGC

TATAAGAAAT

GTGTATGGGC

AAAATCCAGT

GATAAAGACA

AAAAGCTCTG

TGTACCCCTA

TTTCAAGTGT

TA.AGCTCTTC

GACAAGCCCG

GTTGCCCCCC

ACTCCAAATA

TCTTCCAATT

TTTTTGATTA

TGGATATGGT

ACGCTTCTTT

CAGCAAACTA

CTTATTGTAA

GGTTGAATTT

GTTGTTAGCC

TTTGAATAGC

AGGTCTTACC

CGCTAATGGG

CAAGTCGCTA

CGGGCATGCC

CTCTTGGGGT

TGGTATTTTT

TTGGAAAGAG

CCCTAATGCC

TGGGGTGAGA

WO 98/18323 PTU9/97 PCTIUS97/19575 142

GCCAATATCT

AAATTTTTGA

TCGCTTTATT

ACAAGCATAA TGGCGTGGAA TTTGGCGTGA GAGTGCCGCT ACTCATCAAT GCGCGGGTCC TAACGCTACT AACCTTTATT ACCATTTGAA ACGGGATTAT TGGGGTATAA CTACACTTTT TAA 720 780 813 INFORMATION FOR SEQ ID NO:72: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 1317 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genotnic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .1317 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:

ATGGCTTACA

AGCATCTTAG

AATAAAATAC

ATTTCTAGAG

GATAATAGTA

GTTTATGAAG

GATAGAAATA

ACAAACAGCT

GAAACGCATA

AAAGATATTT

CCCAGTATTT

AACAATGAAA

GAATTAGCTA

TATTATTCTT

ATCAATGAAA

CAATTTTTCT

CAAGAAAACA

GCAAAAATTG

AGAGAAATCA

AAGGAGCGTT

GGTAATGAGC

ACTAATACTT

AACCTAACAA

ATAAGGGCGA

AAGAGCCACT

ATCCTATTGA

AAGAAGATGT

CGAATAAAGA

TTGATAGAAA

TAAAAGAATT

AGAAAGCCTT

ACCAAGAAGT

CTAGCGCTGA

ATACCAAACT

AAGAAGTGCA

GGATAGATAA

ATAAACTCAA

TTAATAATGG

GAGATTATTC

AATTGCAAAA

AGCCTTTTAA

ATGACAAATT

GACCAAATTC

CTAACAATAT

AAAGAAGTTA

TGTTGCAACA

CCCTTATGTC

ATGGGCAAAG

CAATTTCTTT

AGGGTTTGAA

TAGAGAATTT

GAAAGAGCAA

AGAAAATGGC

AGAAAGAACA

GTATTTCAAG

GAATACTAAC

TATTTTAATC

AGATGATAAT

AGAAAAC CAT

TTCTATTTTA

TTTAAGAAGC

ATACTATGAA

AGAAATTTTA

GGTAAGCTTG

TAGTGCAAAT

TATTCAAAAT

AAAGAATTAA

AACAATCCTG

GTGAAAACGC

TATTTAAGCT

GCCAATGGTG

AGGCGCATCA

TTTATAAAAG

GGGTTAGAAA

AATGAAATCG

AAAGATGGTG

CTTTACAACA

GACAATGAAG

CTAGAGCAAC

GCGAATTTTG

CTCAGCGCCA

GGCTGGACTA

GCTCTTTTAA

AGCGTTTATG

AGAGACACCA

AGTGCAGCAA

AACAATAACC

AATGATAATA

GAGAGCAACC

TTGAAGAGTC

AAATCAATAA

TTGAAAAACG

AGATAAAAGA

CTAAAAGATA

AAATTGAAAT

TCCAATTGAC

TTAAAGAATA

GATTGGTAAG

AACTGCCTTT

AAGTTAAAAA

AATTGCTTTC

CTTGGAAAAT

ATAACGCTAA

AAGAAGAACA

GTTTAGAAGA

TTAATGGTGA

ACAATTTTGA

TCATTCAAGC

CTATTAAAAA

TAATCATCCA

GAATTTATTT

AGACAAGGCC

AGCAAGCATG

AGTCTATAAG

AAGTTCTCGT

CGATCTGATT

TCTAACCCAC

CCACCATAAT

CGACCATCTT

AGAAATAATC

TGAATCAATA

ACTAGAATTT

AGCAACAAAT

GCATAGGCTT

TAAGATTAAG

AAGCGCTATA

AATCGCTCAA

TGGGAATAAA

AAAAGCTTAT

TAAAGAGGGT

TACAATAGAG

AATTTAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1317 INFORMATION FOR SEQ ID NO:73: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 648 base pairs TYPE: nucleic acid WO 98/18323 PCT/US97/19575 -143- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...648 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73: ATGCAAGCGT TAAAATCATT TTGATGCATA TAGCTATTTT

TACGAAGCTG

AAATTTGAAA

GAAATGCAAG

TATTTAGTGG

GGGCTTTGGA

ACCACCCTAT

CTTTCTGGGG

GTGGCCGGAT

TCATCGGTAG

AAGGGATCGC

AACCTGCATA

ATAACCCTAA

CTGAAGGTTT

TGCCTTTAAT

CTTTTTTATT

CTGGAAGGCT

TTGATGCGAA

GGATTAAAAC

GCTTGAAGTG

CATCATTTTT

CCCTTTTGTG

CAAACAACAC

AATCGTTGAA

AGGGATTACG

GGGCGTAGTT

CACAACGCCA

AGTGGTTAAA

ACGCTATTTG

TAAATGCTCT

ATTACAAAAC

ATTTGGATTG

GCCAACTCCC

AAAATGTCTG

AACAAAGAAT

ATCATGATCC

GGGGGCTTGC

GAAGTGTTTG

GACTTGGCGT

GAGGGTAAAG

AGCGGGTGTT

TCCAGAATCT

GAGGGCTTAA

CTTTCTTTTC

AATCCCAATC

GGCATAAAGA

TAGGCATTTT

TTGTCGCTGG

TCAATCAGCA

TATTTGCTGG

GGTTTTGCTT

GCTCTTAA

AGGCGGCTAT

GTTTGTGCCT

TTTCATGTAT

CATGCAAGAA

AAACCGCACT

GGTGCTTTTG

AATGACGATC

TTTCCCATGG

AGGCTTGTTT

GATGGACCGC

120 180 240 300 360 420 480 540 600 648 INFORMATION FOR SEQ ID NO:74: SEQUENCE CHARACTERISTICS: LENGTH: 186 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...186 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: Met Ile Lys Arg Ile Ala Cys Ile Leu Ser Leu Ser Ala Ser Leu Ala 1 5 10 Leu Ala Gly Glu Val Asn Gly Phe Phe Met Gly Ala Gly Tyr Gin Gin 25 Gly Arg Tyr Gly Pro Tyr Asn Ser Asn Tyr Ser Asp Trp Arg His Gly WO 98/18323 WO 9818323PCTIUS97/19575 144- Asn Asn 65 Thr Gly Gly Tyr Arg 145 Pro Ser Asp Lys Ser Gly Leu Asp 130 Met Met Trp Leu Trp Gly Asp Ile 115 Val Arg Val Tyr Tyr Phe Thr Leu 100 Gly Asn Vai Asn Val 180 Gly Gly Glu Ile Gly Gin Gly Gin 165 Asp Leu Ala 70 His Val1 Vai Thr Asp 150 Gly Tyr Asn 55 Arg Thr Asn Gin Arg 135 Arg Ser Val 40 Phe Vai Lys Leu Leu 120 Phe Ser Lys Phe Lys Tyr Thr Ile 105 Al a Gin Al a Asp Thr 185 Leu Giy Asn 90 Pro Gly Phe Phe Vai 170 Phe Gly Phe 75 Leu Leu Asn Leu Giu 155 Gly Phe Leu Leu Asp Thr Trp 140 Al a Leu Val Asp Thr Lys Trp 125 Asn Gly Ile Giy Trp Tyr Phe 110 Met Leu Val Arg Phe Phe Gly Ala Phe Gly Lys Tyr 175 Ala Asn Gly Leu Pro Gly Phe 160 Tyr INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LEN4GTH: 116 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Heiicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1..-116 (xi) SEQUENCE DESCRIPTION: SEQ ID Leu Met Arg Ile Ile Ile Arg Leu Leu Ser Phe 1 5 10 Leu Lys Leu Ala Leu Ala Ser Leu Met Gly Gly 25 Asn Gly Giu Gly Ser Glu Ile, Val Ala Ile Gly 40 Leu Phe Val Phe Phe Ile Arg Pro Val Ser Phe Arg Glu Glu Tyr Ile Glu Arg Leu Lys Lys Asn 65 70 Ilie Leu Gin Asp Lys Gin Lys Glu Giu Gin Met 90 Lys Lys Glu Arg Giu Ser Arg Gin Lys Gin Asp 100 105 Lys Lys Tyr Ser Met Trp Phe Asp Giu Leu Lys Asn Tyr Vai Pro Arg Tyr Glu 110 Ala Ala Leu Giu Lys Gin Gin WO 98/18323 PCT/US97/19575 145- 115 INFORMATION FOR SEQ ID NO:76: SEQUENCE CHARACTERISTICS: LENGTH: 345 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...345 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: Met Val Lys His Tyr Leu Phe Met Ala Val Ser Gin Val Phe Phe Ser 1 5 10 Phe Phe Leu Val Leu Phe Phe Ile Ser Ser Ile Val Leu Leu Ile Ser 25 Ile Ala Ser Val Thr Leu Val Ile Lys Val Ser Phe Leu Asp Leu Val 40 Gin Leu Phe Leu Tyr Ser Leu Pro Gly Thr Ile Phe Phe Ile Leu Pro 50 55 Ile Thr Phe Phe Ala Ala Cys Ala Leu Gly Leu Ser Arg Leu Ser Tyr 70 75 Asp His Glu Leu Leu Val Phe Phe Ser Leu Gly Val Ser Pro Lys Lys 90 Met Thr Lys Ala Phe Val Pro Leu Ser Leu Leu Val Ser Ala Ile Leu 100 105 110 Leu Ala Phe Ser Leu Ile Leu Ile Pro Thr Ser Lys Ser Ala Tyr Tyr 115 120 125 Gly Phe Leu Arg Gin Lys Lys Asp Lys Ile Asp Ile Asn Ile Arg Ala 130 135 140 Gly Glu Phe Gly Gin Lys Leu Gly Asp Trp Leu Val Tyr Val Asp Lys 145 150 155 160 Thr Glu Asn Asn Ser Tyr Asp Asn Leu Val Leu Phe Ser Asn Lys Ser 165 170 175 Leu Ser Gin Glu Ser Phe Ile Leu Ala Gin Lys Gly Asn Ile Asn Asn 180 185 190 Gin Asn Gly Val Phe Glu Leu Asn Leu Tyr Asn Gly His Ala Tyr Phe 195 200 205 Thr Gin Gly Asp Lys Met Arg Lys Val Asp Phe Glu Glu Leu His Leu 210 215 220 Arg Asn Lys Leu Lys Ser Phe Asn Ser Asn Asp Ala Ala Tyr Leu Gin 225 230 235 240 Gly Thr Asp Tyr Leu Gly Tyr Trp Lys Lys Ala Phe Gly Lys Asn Ala 245 250 255 Asn Lys Asn Gin Lys Arg Arg Phe Ser Gin Ala Ile Leu Val Ser Leu WO 98/18323 WO 9818323PCTIUS97/19575 146- 260 265 270 Phe Pro Leu Ala Ser Val Phe Leu Ile Pro Leu Phe Gly Ile Ala Asn 275 280 285 Pro Arg Phe Lys Thr Asn Trp Ser Tyr Phe Tyr Val Leu Gly Ala Val 290 295 300 Gly Val Tyr Phe Leu Met Val His Val Ile Ser Thr Asp Leu Phe Leu 305 310 315 320 Met Thr Phe Phe Phe Pro Phe Ile Trp Ala Phe Ile Ser Tyr Leu Leu 325 330 335 Phe Arg Lys Phe Ile Leu Lys Arg Tyr 340 345 INFORMATION FOR SEQ ID NO:77: SEQUENCE CHARACTERISTICS: LENGTH: 276 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc feature LOCATION 1. 276 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77: Met Lys Lys Lys Ala Lys Vai Phe Trp Cys Cys Phe 1 Trp Glu Ile Gly Val Lys Leu Asp Asp 145 Asp Gin Leu Ile Leu 50 Asn Arg Val Ser Ser 130 Gin Asn Lys Tyr Aia Aia Al a Tyr Tyr Leu 115 Val Lys Pro Ser Leu Met Asp Ile Asp Arg 100 Asn Ser Tyr Ile His Val Ang Val Leu 70 Lys Giu Lys Ile Ile 150 His Ser Phe Phe Ser 55 Asn Thr Gly Tyr Trp 135 Lys Val1 Met Phe Asp 40 Ala Tyr Lys Leu Giu 120 Val Asn Asn Trp Leu 25 Lys Lys Asp Glu Leu 105 Ile Ser Met Al a Asn S er Asn Asn Tyr 75 Leu Lys Phe Asp Ala 155 Ser Lys Val His Val Ile Leu Thr Pro Ile 140 Sen Gly Ile Lys Ser Lys Ile Leu Glu Asp Phe 125 Al a Gly Sen Tyr Met Asp Ile Thr Al a Gly Tyr 110 Tyr Ser Cys Phe Val Ile Ala Phe Al a Asp Asn Val1 Val Gly Ser Asn 175 Gly Arg Lys Giu Ser Lys Ile Lys Gin Lys Ile 160 Met Asp WO 98/18323 WO 9818323PCT[US97/19575 -147- 180 185 Ile Pro Val Leu Tyr Leu Pro Tyr Ile Phe Met Ser Thr 195 200 205 Arg Thr Thr Gly Phe Leu Tyr Pro Giu Phe Gly Thr Ser 210 215 220 Gly Phe Ile Tyr Leu Gin Pro Phe Tyr Leu Ala Pro Lys 225 230 235 Asp Met Thr Phe Thr Pro Gin Ile Arg Tyr Lys Arg Gly 245 250 Asn Phe Giu Ala Arg Tyr Ile Asn Ser Lys Thr Gin Val 260 265 Cys Ala Leu Phe 275 INFORMATION FOR SEQ ID NO:78: SEQUENCE CHARACTERISTICS: LENGTH: 224 amino acids TYPE: amino acid TOPOLOGY: iinear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .224 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78: 190 Sen Asn Asn Phe Phe 270 Asn Lys Leu Asp Sen Trp 240 Giy Leu 255 Ile Gin Met Ile Arg Leu Lys Gly Leu Asn Lys Thr Leu Lys 1* Ala Leu Glu Leu Giu Asn Lys Met Gin 145 Phe Gly Sen Asp Asn Lys Leu Ile Ala 130 Leu Ile Vai Asp 35 Thr Ser Ile Ile Lys 115 Phe Gin Asp Leu Glu Leu Gly Phe Asn 100 Glu Giu Thr Asp 5 Leu Asp Thr Trp Giu Lys Ile Met Met Trp Gly Leu Ser Asn 70 Cys Giu Lys Lys Leu 150 His Al a Leu Cys 55 Leu .Val Asp Glu Giu 135 Giu Glu Thr Lys 40 Asn Ser Giu Thr Lys 120 His Asn Arg Leu Lys Val Phe 75 Lys Lys Val Giu Asp 155 Gly Met Leu Asp Pro His Giu Leu Phe 140 Asn Ile Thr Ala His Gly Gin Lys Glu Arg 125 Pro Gly Ser Ser Lys Asn Ser Glu Gin Leu 110 Gin Asn Ala Ang Leu Pro Ile Gin Tyr Al a Al a Lys Lys Giu Glu Leu Leu Lys Tyr Arg Leu Lys Phe Lys Ser 160 Asn WO 98/18323 PCT/US97/19575 148- 165 170 175 Thr Tyr Lys Ala Leu Gly Ile Lys Glu Tyr Ser Asp Glu Gly Lys Ile 180 185 190 Leu Pro Leu Ala Lys Glu Val Ile Leu Asp Asn Ile Lys Lys Ile Leu 195 200 205 Lys Lys Ala Leu Met Ile Leu Asp Asn Pro Tyr Leu Leu Trp Leu Val 210 215 220 INFORMATION FOR SEQ ID NO:79: SEQUENCE CHARACTERISTICS: LENGTH: 429 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...429 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79: Met Pro Tyr Ala Leu Arg Lys Arg Phe Phe Lys Arg Leu Leu Leu Phe 1 s 10 is Phe Leu Ile Val Cys Met Ile Asn Leu His Ala Lys Ser Tyr Leu Phe 25 Ser Pro Leu Pro Pro Ala His Gin Gin Ile Ile Lys Thr Glu Pro Cys 40 Ser Leu Glu Cys Leu Lys Asp Leu Met Leu Gin Asn Gin Ile Phe Ser 55 Phe Val Ser Gin Tyr Asp Asp Asn Asn Gin Asp Glu Ser Leu Lys Thr 70 75 Tyr Tyr Lys Asp Ile Leu Asn Lys Leu Asn Pro Val Phe Ile Ala Ser 85 90 Gin Thr Pro Ala Lys Glu Ser Tyr Glu Pro Lys Ile Glu Leu Ala Ile 100 105 110 Leu Leu Pro Lys Lys Val Val Gly Arg Tyr Ala Ile Leu Val Met Asn 115 120 125 Thr Leu Leu Ala Tyr Leu Asn Thr Arg Asn Asn Asp Phe Asn Ile Gin 130 135 140 Val Phe Asp Ser Asp Glu Glu Ser Pro Glu Lys Leu Glu Glu Thr Tyr 145 150 155 160 Lys Glu Ile Glu Lys Glu Lys Phe Pro Phe Ile Ile Ala Leu Leu Thr 165 170 175 Lys Glu Gly Val Glu Asn Leu Leu Gin Asn Thr Thr Ile Asn Thr Pro 180 185 190 Thr Tyr Val Pro Thr Val Asn Lys Thr Gin Leu Glu Asn His Thr Glu 195 200 205 Leu Ser Leu Ser Glu Arg Leu Tyr Phe Gly Gly Ile Asp Tyr Lys Glu WO 98/18323 PCT/US97/19575 -149- 210 215 220 Gin Leu Gly Met Leu Ala Thr Phe Ile Ser Pro Asn Ser Pro Val Ile 225 230 235 240 Glu Tyr Asp Asp Asp Gly Leu Ile Gly Glu Arg Leu Arg Gin Ile Thr 245 250 255 Glu Ser Leu Asn Val Glu Val Lys His Gin Glu Asn Ile Ser Tyr Lys 260 265 270 Gin Ala Thr Ser Phe Ser Lys Asn Phe Arg Lys His Asp Ala Phe Phe 275 280 285 Lys Asn Ser Thr Leu Ile Leu Asn Thr Pro Thr Thr Lys Ser Gly Leu 290 295 300 Ile Leu Ser Gin Ile Gly Leu Leu Glu Tyr Lys Pro Leu Lys Ile Leu 305 310 315 320 Ser Thr Gin Ile Asn Phe Asn Pro Ser Leu Leu Leu Leu Thr Gin Pro 325 330 335 Lys Asp Arg Lys Asn Leu Phe Ile Val Asn Ala Leu Gin Asn Ser Asp 340 345 350 Glu Thr Leu Ile Glu Tyr Ala Ser Leu Leu Glu Ser Asp Leu Arg His 355 360 365 Asp Trp Val Asn Tyr Ser Ser Ala Ile Gly Leu Glu Met Phe Leu Asn 370 375 380 Thr Leu Asp Pro His Phe Lys Lys Ser Phe Gin Glu Ser Leu Glu Asp 385 390 395 400 Asn Gin Val Arg Tyr His Asn Gin Ile Tyr Gin Ala Leu Gly Tyr Ser 405 410 415 Phe Glu Pro Ile Lys Asn Glu Ser Glu Thr Lys Lys Glu 420 425 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 455 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...455 (xi) SEQUENCE DESCRIPTION: SEQ ID Val Leu Lys Phe Gin Lys Leu Pro Leu Leu Phe Val Ser Ile Leu Tyr 1 5 10 Asn Gin Ser Pro Leu Leu Ala Phe Asp Tyr Lys Phe Ser Gly Val Ala 25 Glu Ser Val Ser Lys Val Gly Phe Asn His Ser Lys Leu Asn Ser Lys 40 Glu Gly Ile Phe Pro Thr Ala Thr Phe Val Thr Ala Thr Ile Lys Leu WO 98/18323 PCT/US97/19575 -150- 55 Gin Val Asp Ser Asn Leu Leu Pro Lys Asn Ile Glu Lys His Ser Leu 70 75 Lys Ile Gly Val Gly Gly Ile Leu Gly Ala Leu Ala Tyr Asp Ser Thr 85 90 Lys Thr Leu Ile Asp Gin Ala Thr His Gin Ile Tyr Gly Ser Glu Leu 100 105 110 Phe Tyr Leu Ile Gly Arg Trp Trp Gly Phe Leu Gly Asn Ala Pro Trp 115 120 125 Lys Asp Ser Leu Ile Glu Ser Asp Ala His Thr Arg Asn Tyr Val Leu 130 135 140 Tyr Asn Ser Tyr Leu Phe Tyr Ser Tyr Gly Asp Lys Phe His Leu Lys 145 150 155 160 Leu Gly Arg Tyr Leu Ser Asn Met Asp Phe Met Ser Ser Tyr Thr Gin 165 170 175 Gly Phe Glu Leu Asp Tyr Lys Ile Asn Ser Lys Ile Ala Leu Lys Trp 180 185 190 Phe Ser Ser Phe Gly Arg Ala Leu Ala Phe Gly Gin Trp Ile Arg Asp 195 200 205 Trp Tyr Ala Pro Ile Val Thr'Glu Asp Gly Arg Lys Glu Val Tyr Asp 210 215 220 Gly Ile His Ala Ala Gin Leu Tyr Phe Ser Ser Lys His Val Gin Val 225 230 235 240 Met Pro Phe Ala Tyr Phe Ser Pro Lys Ile Tyr Gly Ala Pro Gly Val 245 250 255 Lys Ile His Ile Asp Ser Asn Pro Lys Phe Lys Gly Leu Gly Leu Arg 260 265 270 Ala Gin Thr Thr Ile Asn Val Ile Phe Pro Val Tyr Ala Lys Asp Leu 275 280 285 Tyr Asp Val Tyr Trp Arg Asn Ser Lys Ile Gly Glu Trp Gly Ala Ser 290 295 300 Leu Leu Ile His Gin Arg Phe Asp Tyr Asn Glu Phe Asn Phe Gly Phe 305 310 315 320 Gly Tyr Tyr Gin Asn Phe Gly Asn Ala Asn Ala Arg Ile Gly Trp Tyr 325 330 335 Gly Asn Pro Ile Pro Phe Asn Tyr Arg Asn Asn Ser Val Tyr Gly Gly 340 345 350 Val Phe Ser Asn Ala Ile Thr Ala Asp Ala Val Ser Gly Tyr Val Phe 355 360 365 Gly Gly Gly Val Tyr Arg Gly Phe Leu Trp Gly Ile Leu Gly Arg Tyr 370 375 380 Thr Tyr Ala Thr Arg Ala Ser Glu Arg Ser Ile Asn Leu Asn Leu Gly 385 390 395 400 Tyr Lys Trp Gly Ser Phe Ala Arg Val Asp Val Asn Leu Glu Tyr Tyr 405 410 415 Val Val Ser Met His Asn Gly Tyr Arg Leu Asp Tyr Leu Thr Gly Pro 420 425 430 Phe Asn Lys Ala Phe Lys Ala Asp Ala Gin Asp Arg Ser Asn Leu Met 435 440 445 Val Ser Met Lys Phe Phe Phe 450 455 INFORMATION FOR SEQ ID NO:81: SEQUENCE CHARACTERISTICS: WO 98/18323 WO 9818323PCTIUS97/19575 151- LENGTH: 282 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION 282 (xi) SEQUENCE DESCRIPTION: SEQ ID, NO:8i: Met Gly Cys Ser Phe Ile Phe Lys Lys Val Arg Val 1 Leu Pro Val Leu His Lys Thr Lys Leu 3.45 Asp ser Asp Thr Ile 225 Leu Thr Gly Val Sen Gin 50 Asp Val Pro Ile Ala 130 Lys Pro Val Phe Sen 210 His Asn Lys Phe Ala Ala Thn Phe Val Tyr Phe 115 Leu Gly Asn Tnp, Ala 195 Thr Glu Ang Giu Lys 275 Leu Glu His Asn Gly Ile 100 Glu Asn Trp Sen Phe 180 Val Asfl Asfl Met Asfl 260 Sen Leu Lys Arg Pro 70 Leu Lys Arg Gin Giy 150 Asn Phe Val Ala Asp 230 Al a Al a Met Sen Lys Met 55 Val1 Met Phe Gly Asp 135 Ile Leu Tyr Gly Ser 215 Lys Val1 Lys Pro 10 Val Leu 25 Asn Asp Thr Ser Ile Val Arg Ile Asp Ala 105 Gin Val Lys Lys Giu Asp Thr Leu 170 Pro Glu 185 Phe Gin Giy Phe Arg Glu Met Lys 250 Arg Asp 265 Lys Lys Ile Ala Ser Gin 75 Gin Leu Leu Ile Leu 155 Val Ser Ala Asn Asp 235 Lys Gly Lys Glu Ala Val Ile Arg Phe 140 Lys Asp Asn.

Ile Sen 220 Aia Ala Tyr Cys Asn His Pro Ser Asn Phe 125 Ser Met Gln Arg Thr 205 Sen Ile Val Ser Ala Gin Val Gin Asp Gin 110 Gin Val Asn Ser Val 190 Tyr Lys His Thr Lys Met Gin Thr Asn Asn Ile Asp Leu Leu Ser 175 Val Thr Sen Lys Glu Met Asn Pro Pro His Leu Gin Glu Asp Lys 160 Gly His Tyr Val Ile 240 Leu 255 Aia Ile Asp Arg Met Lys 270 INFORMATION FOR SEQ ID NO:82: WO 98/18323 PCT/US97/19575 152- SEQUENCE CHARACTERISTICS: LENGTH: 280 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...280 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82: Met Lys Leu Arg Ala Ser Val Leu Ile Gly Val Ala Ile Leu Cys Leu 1 5 10 Ile Leu Ser Ala Cys Ser Asn Tyr Ala Lys Lys Val Val Lys Gin Lys 25 Asn His Val Tyr Thr Pro Val Tyr Asn Glu Leu Ile Glu Lys Tyr Ser 35 40 Glu Ile Pro Leu Asn Asp Lys Leu Lys Asp Thr Pro Phe Met Val Gin 55 Val Lys Leu Pro Asn Tyr Lys Asp Tyr Leu Leu Asp Asn Lys Gin Val 70 75 Val Leu Thr Phe Lys Leu Val His His Ser Lys Lys Ile Thr Leu Ile 90 Gly Asp Ala Asn Lys Ile Leu Gin Tyr Lys Asn Tyr Phe Gin Ala Asn 100 105 110 Gly Ala Arg Ser Asp Ile Asp Phe Tyr Leu Gin Pro Thr Leu Asn Gin 115 120 125 Lys Gly Val Val Met Ile Ala Ser Asn Tyr Asn Asp Asn Pro Asn Asn 130 135 140 Lys Glu Lys Pro Gin Thr Phe Asp Val Leu Gin Gly Ser Gin Pro Met 145 150 155 160 Leu Gly Ala Asn Thr Lys Asn Leu His Gly Tyr Asp Val Ser Gly Ala 165 170 175 Asn Asn Lys Gin Val Ile Asn Glu Val Ala Arg Glu Lys Ala Gin Leu 180 185 190 Glu Lys Ile Asn Gln Tyr Tyr Lys Thr Leu Leu Gin Asp Lys Glu Gin 195 200 205 Glu Tyr Thr Thr Arg Lys Asn Asn Gin Arg Glu Ile Leu Glu Thr Leu 210 215 220 Ser Asn Arg Ala Gly Tyr Gin Met Arg Gin Asn Val Ile Ser Ser Glu 225 230 235 240 Ile Phe Lys Asn Gly Asn Leu Asn Met Gin Ala Lys Glu Glu Glu Val 245 250 255 Arg Glu Lys Leu Gin Glu Glu Arg Glu Asn Glu Tyr Leu Arg Asn Gin 260 265 270 Ile Arg Ser Leu Leu Ser Gly Lys 275 280 WO 98/18323 PCT/US97/19575 153- INFORMATION FOR SEQ ID NO:83: SEQUENCE CHARACTERISTICS: LENGTH: 393 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...393 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83: Met Arg Lys Leu Phe Ile Pro Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 Asn Glu Lys Asn Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr Gly Leu 20 25 Leu Glu Gly Thr Gin Thr Gin Glu Lys Arg His Thr Thr Thr Lys Asn 40 Thr Tyr Ala Thr Tyr Asn Tyr Leu Pro Thr Asp Thr Ile Leu Lys Arg 55 Ala Ala Asn Leu Phe Thr Asn Ala Glu Ala Ile Ser Lys Leu Lys Phe 70 75 Ser Ser Leu Ser Pro Val Arg Val Leu Tyr Met Tyr Asn Gly Gin Leu 90 Thr Ile Glu Asn Phe Leu Pro Tyr Asn Leu Asn Asn Val Lys Leu Ser 100 105 110 Phe Thr Asp Ala Gin Gly Asn Val Ile Asp Leu Gly Val Ile Glu Thr 115 120 125 Ile Pro Lys His Ser Lys Ile Val Leu Pro Gly Glu Ala Phe Asp Ser 130 135 140 Leu Lys Ile Asp Pro Tyr Thr Leu Phe Leu Pro Lys Ile Glu Ala Thr 145 150 155 160 Ser Thr Ser Ile Ser Asp Ala Asn Thr Gin Arg Val Phe Glu Thr Leu 165 170 175 Asn Lys Ile Lys Thr Asn Leu Val Val Asn Tyr Arg Asn Glu Asn Lys 180 185 190 Phe Lys Asp His Glu Asn His Trp Glu Ala Phe Thr Pro Gin Thr Ala 195 200 205 Glu Glu Phe Thr Asn Leu Met Leu Asn Met Ile Ala Val Leu Asp Ser 210 215 220 Gin Ser Trp Gly Asp Ala Ile Leu Asn Ala Pro Phe Glu Phe Thr Asn 225 230 235 240 Ser Pro Thr Asp Cys Asp Asn Asp Pro Ser Lys Cys Val Asn Pro Gly 245 250 255 Thr Asn Gly Leu Val Asn Ser Lys Val Asp Gin Lys Tyr Val Leu Asn 260 265 270 WO 98/18323 PCT/US97/19575 -154- Lys Gin Asp Ile Val Asn Lys Phe Lys Asn Lys Ala Asp Leu Asp Val 275 280 285 Ile Val Leu Lys Asp Ser Gly Val Val Gly Leu Gly Ser Asp Ile Thr 290 295 300 Pro Ser Asn Asn Asp Asp Gly Lys His Tyr Gly Gin Leu Gly Val Val 305 310 315 320 Ala Ser Ala Leu Asp Pro Lys Lys Leu Phe Gly Asp Asn Leu Lys Thr 325 330 335 Ile Asn Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr 340 345 350 Lys Gly Tyr Gly His Asn Gly Asn Met Thr Tyr Gin Arg Val Pro Val 355 360 365 Thr Lys Asp Gly Gin Val Glu Lys Asp Ser Asn Gly Lys Pro Lys Asp 370 375 380 Ser Asp Gly Leu Pro Tyr Asn Val Cys 385 390 INFORMATION FOR SEQ ID NO:84: SEQUENCE CHARACTERISTICS: LENGTH: 270 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...270 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84: Met Lys Lys Phe Val Ala Leu Gly Leu Leu Ser Ala Val Leu Ser Ser 1 5 10 Ser Leu Leu Ala Glu Gly Asp Gly Val Tyr Ile Gly Thr Asn Tyr Gin 25 Leu Gly Gin Ala Arg Leu Asn Ser Asn Ile Tyr Asn Thr Gly Asp Cys 40 Thr Gly Ser Val Val Gly Cys Pro Pro Gly Leu Thr Ala Asn Lys His 50 55 Asn Pro Gly Gly Thr Asn Ile Asn Trp His Ser Lys Tyr Ala Asn Gly 70 75 Ala Leu Asn Gly Phe Gly Leu Asn Val Gly Tyr Lys Lys Phe Phe Gin 90 Phe Lys Ser Leu Asp Met Thr Ser Lys Trp Phe Gly Phe Arg Val Tyr 100 105 110 Gly Leu Phe Asp Tyr Gly His Ala Asp Leu Gly Lys Gin Val Tyr Ala 115 120 125 Pro Asn Lys Ile Gin Leu Asp Met Val Ser Trp Gly Val Gly Ser Asp 130 135 140 WO 98/18323 PCT/US97/19575 -155- Leu Leu Ala Asp Ile Ile Asp Lys Asp Asn Ala Ser Phe Gly Ile Phe 145 150 155 160 Gly Gly Val Ala Ile Gly Gly Asn Thr Trp Lys Ser Ser Ala Ala Asn 165 170 175 Tyr Trp Lys Glu Gin Ile Ile Glu Ala Lys Gly Pro Asp Val Cys Thr 180 185 190 Pro Thr Tyr Cys Asn Pro Asn Ala Pro Tyr Ser Thr Asn Thr Ser Thr 195 200 205 Val Ala Phe Gin Val Trp Leu Asn Phe Gly Val Arg Ala Asn Ile Tyr 210 215 220 Lys His Asn Gly Val Glu Phe Gly Val Arg Val Pro Leu Leu Ile Asn 225 230 235 240 Lys Phe Leu Ser Ala Gly Pro Asn Ala Thr Asn Leu Tyr Tyr His Leu 245 250 255 Lys Arg Asp Tyr Ser Leu Tyr Leu Gly Tyr Asn Tyr Thr Phe 260 265 270 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 140 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...140 (xi) SEQUENCE DESCRIPTION: SEQ ID Met His Pro Ile Met Phe Ala Tyr Ile Ala Asn Ala Leu Ala Gin Ala 1 5 10 Arg Lys Ile Asn Gly Thr Leu Cys Met Ala Phe Gin Lys Ile Ser Gin 25 Val Lys Glu Leu Gly Ile Asp Lys Ala Lys Ser Leu Ile Gly Asn Leu 40 Ser Gin Val Ile Ile Tyr Pro Thr Lys Asp Thr Asp Glu Leu Ile Glu 50 55 Cys Gly Val Pro Leu Ser Asp Ser Glu Ile Asn Phe Leu His Asn Thr 70 75 Asp Met Arg Ala Arg Gin Val Leu Val Lys Asn Ile Val Thr Asn Ala 90 Ser Ala Phe Ile Glu Ile Asp Leu Lys Lys Ile Cys Lys Asn Tyr Phe 100 105 110 Ile Phe Leu Ile Ala Met Leu Val Ile Glu Lys Ser Ser Met Ile Leu 115 120 125 Lys Lys Gin Thr Lys Lys Leu Ile Arg Lys Ser Ile 130 135 140 WO 98/18323 PCT/US97/19575 156- INFORMATION FOR SEQ ID NO:86: SEQUENCE CHARACTERISTICS: LENGTH: 256 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...256 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86: Met Leu Gly Ser Val Lys Lys Ala Val Phe Arg Val Leu Cys Leu Gly 1 5 10 Ala Leu Cys Leu Cys Gly Gly Leu Met Ala Glu Gin Asp Pro Lys Glu 20 25 Leu Ile Phe Ser Gly Ile Thr Ile Tyr Thr Asp Lys Asn Phe Thr Arg 40 Ala Lys Lys Tyr Phe Glu Lys Ala Cys Lys Ser Asn Asp Ala Asp Gly 55 Cys Ala Ile Leu Arg Glu Val Tyr Ser Ser Gly Lys Ala Ile Ala Arg 70 75 Glu Asn Ala Arg Glu Ser Ile Glu Lys Ala Leu Glu His Thr Ala Thr 90 Ala Lys Val Cys Lys Leu Asn Asp Ala Glu Lys Cys Lys Asp Leu Ala 100 105 110 Glu Phe Tyr Phe Asn Val Asn Asp Leu Lys Asn Ala Leu Glu Tyr Tyr 115 120 125 Ser Lys Ser Cys Lys Leu Asn Asn Val Glu Gly Cys Met Leu Ser Ala 130 135 140 Thr Phe Tyr Asn Asp Met Ile Lys Gly Leu Lys Lys Asp Lys Lys Asp 145 150 155 160 Leu Glu Tyr Tyr Ser Lys Ala Cys Glu Leu Asn Asn Gly Gly Gly Cys 165 170 175 Ser Lys Leu Gly Gly Asp Tyr Phe Phe Gly Glu Gly Val Thr Lys Asp 180 185 190 Phe Lys Lys Ala Phe Glu Tyr Ser Ala Lys Ala Cys Glu Leu Asn Asp 195 200 205 Ala Lys Gly Cys Tyr Ala Leu Ala Ala Phe Tyr Asn Glu Gly Lys Gly 210 215 220 Val Ala Lys Asp Glu Lys Gin Thr Thr Glu Asn Leu Glu Lys Ser Cys 225 230 235 240 Lys Leu Gly Leu Lys Glu Ala Cys Asp Ile Leu Lys Glu Gln Lys Gin 245 250 255 INFORMATION FOR SEQ ID NO:87: WO-98/18323 WO 9818323PCTIUS97119575 -157- SEQUENCE CHARACTERISTICS: LENGTH: 242 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .242 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87: Met Lys Lys Phe Phe Ser Gln Ser Leu Leu Ala Leu Ile Ile Sen Met 1 Asn Tyr Gin Gln Asp Sen Asn Leu Gly 145 Sen Ala Gly Lys Asp 225 Thn Al a Leu Ala s0 Phe Tyr Glu Ang Thr 330 Ile Tnp Leu Ala Phe 210 Ile Phe Val Gin 35 Thr Phe Ala Al a Leu 115 Tyr Met Leu Val Ang 195 Pro Giy Ser Gly Asn Phe His Al a 100 Thr Gly Sen Met Ser 180 Leu Met Phe 5 Gly Gin Ala Glu Ala Gin Asn.

Gly Leu Ala 165 Lys Arg Leu Arg Met Al a Thr Lys 70 Asn Val Ile Ala Gly 150 Thr Lys Ile Lys Arg 230 Asp Gin Ile 55 His Ser Ala Ala Met 135 Ala Pro Ala Leu Lys 215 Val1 Gly Met 40 Lys Phe Ile Ser Asp 120 Asp Phe Ser Thr Lys 200 Asn Tyr Asn 25 His Gly Gly Lys Gin 105 Pro Val Gly Phe Ser 185 His Pro Ser 10 Gly Val Phe Ala Asp Ile Phe Asp Ala Leu Arg Leu 75 Leu Lys Asn 90 Ile Leu Gly Arg Thr Phe Met Val Asn 140 Gly Ile Gin 155 Glu Gly Ile 170 Phe Gin Phe Ser Ser Ile Tyr Ile Thr 220 Leu Asn Leu Tyr Pro Lys Glu 125 Val Leu Leu Leu Glu 205 Al a Gly Ser Leu Gly Asn Gin 110 Pro Ile Ala Val Phe 190 Ala Lys Ala Gin Gly Phe Tyr Glu Asn Asn Gly Glu 175 Asn Gly Asn Gly Lys Tyr Phe Asn Ile Met Asn Asn 160 Gin Val1 Val Leu Phe 240 Trp, Tyr Val Asn Tyr Val INFORMATION FOR SEQ ID NO:88: SEQUENCE CHARACTERISTICS: WO-98/18323 WO .9818323PCTIUS97/19575 158 LENGTH: 267 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 267 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88: Met Asn Tyr Pro Asn Leu Pro Asn Sen Ala Leu Giu Ile Ser Glu Gin 1 Pro Ala Lys Lys Leu Ang Val Lys Sen 145 Ile Asn Asn Gin Thn 225 Giu His Giu Leu Cys 50 Asn Thr Phe Thr Lys 130 Tyr Thr Asn Ile Thr 210 Gin Lys Tyr Val1 Arg Ile Aia Asn Phe Asn 115 Leu Gin Lys Al a Thr 195 Gin Ile Thr Gin Lys Ser Val Asn Ala Ser 100 Thn Giu Ile Asn Asn 180 Giu Ala Asn Gin Asn 260 5 Giu Asn Arg Giu Gly Giu Leu Asn Phe Lys 165 Asn Ala Ile Ala Ala 245 Ile Ile Ala Ile Ile 70 Giu Phe Asn Gin Leu 150 Thn Giu Lys Thr Asn 230 Thr Asp Thn His Leu 55 Asp Ser Asn Ala Leu 135 Asn Gin Ile Thr Asn 215 Lys Ser Phe Asn Phe 40 Giu Ser Leu Thn Asn 120 Ile Gin Ser Ser Asn 200 Ile Gin Giu Phe Giu 25 Ser Val Sen Lys Ser 105 Ala Giu Ala Leu Asn 185 Ala Asn Giu Ile Giu 265 10 Leu Giu Leu Leu Leu 90 Met Giu Thr Arg Giu 170 Asn Asn Giu Ala Thr 250 Phe Leu Gin Leu Arg 75 Lys His Asn Thr Asp Ala Gin Asn Al a Ile 235 Giu Glu Lys Val Sen Asn Met Al a Ile Thr 140 Asn Ile Thn Glu Lys 220 Asn Ala Gin Giu Leu Sen Lys Asn Lys 125 Arg Al a Thn Gin Ile 205 Giu Asn Lys Leu Leu Asp Ile Glu Glu 110 Ser Leu Asn Gin Ala 190 Sen Ser Ile Lys Gin Sen Phe Glu Tyr Gin Giu Leu Asn Ala 175 Ile Asn Ala Thr Thr 255 Asn Leu Phe Trp Giu Giu Ile Thn Gin 160 Lys Thr Asn Thr Gin 240 Asp INFORMATION FOR SEQ ID NO:89: SEQUENCE CHARACTERISTICS: WO 98/18323 PCT/US97/19575 -159- LENGTH: 544 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...544 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89: Val Ile Glu Thr Ile Pro Lys His Ser Lys Ile Val Leu Pro Gly Glu 1 5 10 Ala Phe Asp Ser Leu Lys Glu Ala Phe Asp Lys Ile Asp Pro Tyr Thr 25 Phe Phe Phe Pro Lys Phe Glu Ala Thr Ser Thr Ser Ile Ser Asp Thr 40 Asn Thr Gin Arg Val Phe Glu Thr Leu Asn Asn Ile Lys Thr Asn Leu 50 55 Ile Met Lys Tyr Ser Asn Glu Asn Pro Asn Asn Phe Asn Thr Cys Pro 70 75 Tyr Asn Asn Asn Gly Asn Thr Lys Asn Asp Cys Trp Gin Asn Phe Thr 90 Pro Gin Thr Ala Glu Glu Phe Thr Asn Leu Met Leu Asn Met Ile Ala 100 105 110 Val Leu Asp Ser Gin Ser Trp Gly Asp Ala Ile Leu Asn Ala Pro Phe 115 120 125 Glu Phe Thr Asn Ser Ser Thr Asp Cys Asp Ser Asp Pro Ser Lys Cys 130 135 140 Val Asn Pro Gly Val Asn Gly Arg Val Asp Thr Lys Val Asp Gin Gin 145 150 155 160 Tyr Ile Leu Asn Lys Gin Gly Ile Ile Asn Asn Phe Arg Lys Lys Ile 165 170 175 Glu Ile Asp Ala Val Val Leu Lys Asn Ser Gly Val Val Gly Leu Ala 180 185 190 Asn Gly Tyr Gly Asn Asp Gly Glu Tyr Gly Thr Leu Gly Val Glu Ala 195 200 205 Tyr Ala Leu Asp Pro Lys Lys Leu Phe Gly Asn Asp Leu Lys Thr Ile 210 215 220 Asn Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr Lys 225 230 235 240 Gly Tyr Gly His Asn Gly Asn Met Thr Tyr Gin Arg Val Pro Val Thr 245 250 255 Lys Asp Gly Gin Val Glu Lys Asp Ser Asn Gly Lys Pro Lys Asp Ser 260 265 270 Asp Gly Leu Pro Tyr Asn Val Cys Ser Leu Tyr Gly Gly Ser Asn Gin 275 280 285 Pro Ala Phe Pro Ser Asn Tyr Pro Asn Ser Ile Tyr His Asn Cys Ala 290 295 300 WO 98/18323 PCT/US97/19575 160- Asp Val Pro Ala Gly Phe Leu Gly Val Thr Ala Ala Val Trp Gin Gin 305 310 315 320 Leu Ile Asn Gin Asn Ala Leu Pro Ile Asn Tyr Ala Asn Leu Gly Ser 325 330 335 Gin Thr Asn Tyr Asn Leu Asn Ala Ser Leu Asn Thr Gin Asp Leu Ala 340 345 350 Asn Ser Met Leu Ser Thr Ile Gin Lys Thr Phe Val Thr Ser Ser Val 355 360 365 Thr Asn His His Phe Ser Asn Ala Ser Gin Ser Phe Arg Ser Pro Ile 370 375 380 Leu Gly Val Asn Ala Lys Ile Gly Tyr Gin Asn Tyr Phe Asn Asp Phe 385 390 395 400 Ile Gly Leu Ala Tyr Tyr Gly Ile Ile Lys Tyr Asn Tyr Ala Lys Ala 405 410 415 Val Asn Gin Lys Val Gin Gin Leu Ser Tyr Gly Gly Gly Ile Asp Leu 420 425 430 Leu Leu Asp Phe Ile Thr Thr Tyr Ser Asn Lys Asn Ser Pro Thr Gly 435 440 445 Ile Gin Thr Lys Arg Asn Phe Ser Ser Ser Phe Gly Ile Phe Gly Gly 450 455 460 Leu Arg Gly Leu Tyr Asn Ser Tyr Tyr Val Leu Asn Lys Val Lys Gly 465 470 475 480 Ser Gly Asn Leu Asp Val Ala Thr Gly Leu Asn Tyr Arg Tyr Lys His 485 490 495 Ser Lys Tyr Ser Val Gly Ile Ser Ile Pro Leu Ile Gin Arg Lys Ala 500 505 510 Ser Val Val Ser Ser Gly Gly Asp Tyr Thr Asn Ser Phe Val Phe Asn 515 520 525 Glu Gly Ala Ser His Phe Lys Val Phe Phe Asn Tyr Gly Gly Cys Phe 530 535 540 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 356 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...356

I-

(xi) SEQUENCE DESCRIPTION: SEQ ID Leu Met Lys Ser Ile Leu Leu Phe Met Ile Phe Val Val Cys Gin Leu 1 5 10 Glu Gly Lys Lys Phe Ser Gin Asp Asn Phe Lys Val Asp Tyr Asn Tyr 20 25 WO 98/18323 WO 9818323PCTIUS97/19575 161 Tyr Leu Arg Lys Gin Asp Leu Ser Trp, Thr Tyr Ile Thr Asp 145 Ile Asn Gly Asn Lys 225 Leu Ala Asp His Tyr 305 Asn Gly Arg Asn Val Tyr His Ser Leu 130 Pro Tyr Phe Gly Gin 210 Asp Cys Tyr Tyr His 290 Asp Pro Leu Leu Ala Asp Phe Pro Phe 115 Tyr Gin Val Ser Aila 195 Phe Val Phe Trp, Met 275 Phe Arg Phe Tyr Asn 355 Trp Phe Leu Asn 100 Arg Leu Ser Tyr Giu 180 Gln Pro Arg Val Pro 260 Gly Giu Trp Val Glu 340 Pro Tyr Al a Pro Ile Val Ala Ala Pro 165 Ile Cys Gly Trp Leu 245 Tyr Tyr Leu His Gly 325 Tyr Leu Lys 70 Phe Asn Pro Tyr Pro iso Ile Trp, Tyr Gin Gly 230 Val Val Gly Gin Gly 310 Ile Asp Pro 55 Lys Tyr Pro Val Thr 135 Met Asn Ile Gin Pro 215 Gly Trp Pro Asn Leu 295 Ala Tyr Val His Ile 40 Pro Gin Tyr Leu His Ser Tyr Gin 105 Phe Arg 120 Gin Thr Arg Met Phe Lys Gly Trp 185 Pro Phe 200 Val Ile Cys Xaa Glu Lys Tyr Asp 265 Ala Lys 280 Tyr Asp Phe Arg Ala Gin Phe Ser 345 Ile Lys Asn Phe 90 Arg His Asn Ile Pro 170 Gin Asn Val Ser Gly 250 Gin Ile Ile Leu Trp 330 Asn Thr Pro Met Pro Giu Leu Phe 140 Phe Giy Ile Giu Asp 220 Xaa Leu Asn Tyr Thr 300 Tyr Asn Ile Gin Lys Asp Ile Phe Trp 125 Gin Met Gly Ser Gly 205 Tyr Xaa Lys Pro Arg 285 Gin Thr Gly Gly Asn Giu Tyr Phe Lys 110 Thr Ile Pro Lys Asn 190 Asn Asn Gly Ile Gin 270 Arg Tyr Tyr Tyr Val 350 Asp His Leu Gin Phe Lys Tyr Glu Ile 175 Gly Pro Giy Asn Met 255 Leu Gly Trp Arg Gly 335 Gly Leu Ser Gly Trp Gin Gly Asn Leu 160 Gly Vai Glu Gin Xaa 240 Vai Ile Arg Arg Ile 320 Asp Ile INFORMATION FOR SEQ ID NO:9i: SEQUENCE CHAR~ACTERISTICS: LENGTH: 675 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: WO 98/18323 WO 9818323PCTIUS97/19575 162- ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc feature LOCATION 1. 675 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9i: Leu Ser Lys Gly Leu Ser Ile Giy Asn Lys Ile Ile 1 Leu Arg ser Tyr Arg His Leu ser Ile 145 Val Glu Asn Giy Thr 225 Ile Ser Lys Giu Val 305 Leu Thr Asp Ile Val Leu Thr Giu Val Thr Leu 130 Sen Tyr Val Giu Lys 210 Giu Leu His Thr Lys 290 Ala Leu Leu Ile Val Lys His Ser Ile Al a Leu 115 Gly Lys Gly Val Ile 195 Vai Ile Giu Lys Giu 275 Asp Ala Met Ser Lys Ile Giu Phe Met Lys Gly 100 Leu Ser Ser Val Gly 180 Thr Leu Tyr Asn Glu 260 Sen Lys Ser Arg His 340 Leu 5 Val Ile Lys Gly Ile 85 Val Arg Asn Leu Asp 165 Val Lys Leu Lys Gly 245 Asn Lys Val Al a Al a 325 Phe Val Cys Leu Val Ile 70 Gin Ser Asp Pro Pro 150 Ile Leu Asn Sen Ser 230 Ser Phe Asp Tyn Ile 310 Ile Phe Glu Val Lys Lys Val Leu Met Asn Leu 135 Tyr Leu Met Ang Al a 215 Vai Lys Leu Asn Glu 295 Met Val1 Lys Ala Ser Glu 40 Giu Lys Leu Phe Asp 120 Ala Tyr Leu Ile Ser 200 Asn Pro Al a Ala Leu 280 Gin Val Sen Leu Arg 10 Ile Leu 25 Ser Ala Val Gin Glu .Met Lys Asn 90 Phe Lys 105 Thr Ile Gin Lys Ang Lys Pro Leu 170 Phe Phe 185 Asp Leu Lys Ser Lys Ala Thr Leu 250 Val Giu 265 Asn Trp Val Gly Leu Ala Asn Arg 330 Leu Asn 345 Ser Asn Gly Leu Ser Leu 75 Phe Asp Lys Ala Met 155 Phe Sen Phe Leu Thr 235 Giu Thr Met Ser Leu 315 Leu Asn Asp Leu Ser Ser Leu Glu Leu Glu Met 125 Lys Asn Giu Asp Ile 205 Asp Glu Leu Lys Ala 285 Ang Ile Val Al a Leu Cys Leu Met Giu Asp Ala Asp 110 Glu Asn Gly Asn Sen 190 Gly Lys Val Asp Met 270 Leu Phe Ala Val1 His 350 Gly Val1 Asn Gin Asn Thr Asn Leu Asn Lys Ala Thr 175 Phe Val Ser Met Pro 255 Leu Ile Val1 Ile Sen 335 Ser Arg Al a Ser Asp Thr Lys Ser Arg Pro Giu Giu 160 Gin Ser Lys Ile Al a 240 Phe Gly Ile Val Thr 320 Ser Ser Met 355 360 365 Gin Thr Ala Ile Asn Lys Asn Ile Leu Gin Thr Gin Lys Thr Met Gin WO 98/18323 PCT/US97/19575 -163- 370 375 380 Glu Asp Arg Gin Ala Val Gln Asp Thr Ile Lys Val Val Ser Asp Val 385 390 395 400 Lys Ala Gly Asn Phe Ala Val Arg Ile Thr Ala Glu Pro Ala Ser Pro 405 410 415 Asp Leu Lys Glu Leu Arg Asp Ala Leu Asn Gly Ile Met Asp Tyr Leu 420 425 430 Gin Glu Ser Val Gly Thr His Met Pro Ser Ile Phe Lys Ile Phe Glu 435 440 445 Ser Tyr Ser Gly Leu Asp Phe Arg Gly Arg Ile Gin Asn Ala Ser Gly 450 455 460 Arg Val Glu Leu Val Thr Asn Ala Leu Gly Gin Glu Ile Gin Lys Met 465 470 475 480 Leu Glu Thr Ser Ser Asn Phe Ala Lys Asp Leu Ala Asn Asp Ser Ala 485 490 495 Asn Leu Lys Glu Cys Val Gin Asn Leu Glu Lys Ala Ser Asn Ser Gin 500 505 510 His Lys Ser Leu Met Glu Thr Ser Lys Thr Ile Glu Asn Ile Thr Thr 515 520 525 Ser Ile Gin Gly Val Ser Ser Gin Ser Glu Ala Met Ile Glu Gin Gly 530 535 540 Lys Asp Ile Lys Ser Ile Val Glu Ile Ile Arg Asp Ile Ala Asp Gin 545 550 555 560 Thr Asn Leu Leu Ala Leu Asn Ala Ala Ile Glu Ala Ala Arg Ala Gly 565 570 575 Glu His Gly Arg Gly Phe Ala Val Val Ala Asp Glu Val Arg Lys Leu 580 585 590 Ala Glu Arg Thr Gin Lys Ser Leu Ser Glu Ile Glu Ala Asn Ile Asn 595 600 605 Ile Leu Val Gin Ser Ile Ser Asp Thr Ser Glu Ser Ile Lys Asn Gin 610 615 620 Val Lys Glu Val Glu Glu Ile Asn Ala Ser Ile Glu Ala Leu Arg Ser 625 630 635 640 Val Thr Glu Gly Asn Leu Lys Ile Ala Ser Asp Ser Leu Glu Ile Ser 645 650 655 Gin Glu Ile Asp Lys Val Ser Asn Asp Ile Leu Glu Asp Val Asn Lys 660 665 670 Lys Gin Phe 675 INFORMATION FOR SEQ ID NO:92: SEQUENCE CHARACTERISTICS: LENGTH: 271 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/18323 WO 9818323PCTIUS97/19575 -164- NAME/KEY: misc-feature LOCATION 1...271 SEQUENCE DESCRIPTION: SEQ ID NO: 92: Met Asn Ile Phe Lys Arg Ile Ile Cys Val Thr Ala 1 Phe His Ala Lys 65 Leu Leu Asn Ilie Al a 145 Ala Lys Pro Al a Ser 225 .Glu Lys Asn Ilie Ile Val Asp Arg His 115 Asn Gin Lys Pro Val1 195 Gin Tyr Ilie Ile Leu Thr Leu Ile Gly Phe 100 Val Leu Gly Asp Tyr 180 Leu Ala Ala Lys Leu 260 5 Leu Arg Gin Val Ser Asn Giu Lys Arg Pro 165 Asn Gly Lys Asn Al a 245 Asp Asp Glu Ser S er 70 Leu Leu Pro Lys Ala 150 Ser Ile Asp Leu Leu 230 Leu Thr Ala Leu Val Phe Asp Asp Leu Gly 135 Leu Asn Lys Val1 Thr 215 Val Ile Tyr Lys Lys 40 Val Thr Ala Arg Arg 120 Ser Ile Leu Ile Asp 200 Gly Ala Giu Lys His 25 Val Asp Asp Asn Lys 105 Phe Vai Leu Tyr Lys 185 Gly Ala Ser Ala Gly 265 10 His Gly Asp Tyr Tyr 90 Met Tyr Ile Leu Ala 170 Pro Al a Leu Arg Leu 250 Ala Lys Ala Leu Val 75 Phe His Ser Al a His 155 Thr Leu Ile Phe Glu 235 Gin Ile Glu Asn Lys Leu Gin Leu Gin Val 140 Lys Glu Giu Ile Ser 220 Asp Ser Ile Ile Lys Pro Giu Pro His Val Lys 125 Pro Gin Phe Ala Thr 205 Glu Asn Giu Pro Val Lys Vai Lys Asn Arg Gly 110 Ile Asn Gly Asp Ala 190 Gly Asp Al a Lys Ala 270 Leu Giu Pro Gly Leu Pro Leu Thr Asp Leu Ile 175 Leu Asn Lys Gin Thr 255 Phe Gly Asp His Ile Al a Tyr Ala Asp Pro Ile 160 Val Leu Tyr Asp Asp 240 Arg INFORMATION FOR SEQ ID N0:93: SEQUENCE CHARACTERISTICS: LENGTH: 161 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/18323 PCT/US97/19575 165- NAME/KEY: misc feature LOCATION 1...161 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93: Met Phe Phe Lys Thr Tyr Gin Lys Leu Leu Gly Ala Ser Cys Leu Ala 1 Leu Glu Asp Val 65 Gin Tyr Ile Asn Glu 145 Lys Leu Ile Ile Phe Thr Ile Gin 115 Gly Glu Val Ala Thr Val Pro Phe 100 Leu Glu Ile Cys Ser Gin Val Ser Gin Gin Leu Thr 150 Asn Gly Val Glu Gin Lys Gly 120 Gly Lys Gly 25 Thr Lys Thr Asp Gly 105 Val Ile Gly 10 Gly Phe Leu Phe Phe Leu Met Ser Ala Gly Ile Arg Met Asp Asn Glu Gly 140 Thr Ser Ser Asn Val Ala Ala 110 Gin Asn Asn Pro Lys Cys Leu Ser Asn Thr Ile Phe INFORMATION FOR SEQ ID NO:94: Met 1 Ala Leu Glu SEQUENCE CHARACTERISTICS: LENGTH: 337 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1,..337 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94: Ile Arg Leu Lys Gly Leu Asn Lys Thr Leu 5 10 Gly Val Leu Leu Gly Ala Thr Ala Pro Leu 25 Ser Asp Glu Asp Leu Leu Lys Arg Val Lys 40 Asp Thr Leu Thr Ser Cys Asn Ala Lys Val Lys Thr Ser Leu Leu Met Ala Lys Pro Leu Leu His Asn Ile Lys Asp Gly Ser Gin Tyr

V

WO 98/18323 PCT/US97/19575 -166- Leu Giu Asn Lys Met Gin 145 Phe Thr Leu Giu Met 225 Gin Leu Gly Trp, Ile 305 Ala His Ser Ile Ile Lys 115 Phe Gin Asp Lys Phe 195 Ser Giy His Asn Asn 275 Phe Giu Ile Giy Phe Asn 100 Glu Giu Thr Asp Ala 180 Gly Thr Glu Ser Met 260 Met Phe Cys Gly Trp, Giu 85 Lys Ile Met Met Trp 165 Leu Giu Tyr Asn Ser 245 Ile Glu Gly Ile Ile 325 Asn 70 Cys Giu Lys Lys Leu 150 His Gly Arg Asp Asp 230 Asn Giu Ile Lys Lys 310 Val Leu Val1 Asp Giu Giu 135 Giu Glu Ile Ser Thr 215 Tyr Asn Leu Asp Al a 295 Asn Trp Ser Giu Thr Lys 120 His Asn Arg Lys Tyr 200 Arg Lys Ile Thr Giy 280 Lys Lys Lys Lys Giu Giu 105 Ala Ser Ala Phe Giu 185 Ile Gin Ile Lys Asn 265 Ser Val1 Val Lys Giu Giu 90 Asp Lys Lys Phe Gly 170 Tyr Arg Thr Thr Pro 250 Ile Lys Pro Lys Asn 330 Phe 75 Lys Lys Val Giu Asp 155 Gly Ser Gin Leu Trp 235 Leu Lys Tyr Giu Ser 315 Thr Pro His Gi u Leu Phe 140 Asn Ile Asp Tyr Ser 220 Leu Met Lys Pro Thr 300 Tyr Tyr Gin Lys Giu Arg i2 Pro Giy Ser Giu Lys 205 Ala Lys Ser Giu Ile 285 Trp Asp Ser Glu Gin Leu 110 Gin Asn Ala Arg Giy 190 Lys Met Pro Asn.

Tyr 270 His Arg Asn Ile Tyr Ala Al a Lys Lys Glu Giu 175 Lys Asp Ala Lys Thr 255 Val Lys Asn.

Thr Ser 335 Arg Leu Lys Phe Lys Ser 160 Asn.

Ile Phe Asn.

Tyr 240 Glu Met Asp Lys Thr 320 His INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 4i6 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .416 WO 98/18323 PCT/US97/19575 -167- (xi) SEQUENCE DESCRIPTION: SEQ ID Met Lys Lys Leu Val Phe Ser Met Leu Leu Cys Cys Lys Ser Val Phe 1 5 10 Ala Glu Gly Glu Thr Pro Leu Ile Val Asn Asp Pro Glu Thr His Val 25 Ser Gin Ala Thr Ile Ile Gly Lys Met Val Asp Ser Ile Lys Arg Tyr 40 Glu Glu Ile Ile Ser Lys Ala Gin Ala Gin Val Asn Gin Leu Gin Lys 55 Val Asn Asn Met Ile Asn Thr Thr Asn Ser Leu Ile Ser Ser Ser Ala 70 75 Ile Thr Leu Ala Asn Pro Met Gin Val Leu Gin Asn Ala Gin Tyr Gin 85 90 Ile Glu Ser Ile Arg Tyr Asn Tyr Glu Asn Leu Lys Gin Ser Ile Glu 100 105 110 Asn Trp Asn Ala Gin Asn Leu Leu Arg Asn Lys Tyr Leu Gin Gin Gin 115 120 125 Cys Pro Trp Leu Asn Val Asn Ala Leu Thr Asn Asn Lys Ile Val Asn 130 135 140 Leu Lys Asp Leu Asn Asn Leu Ile Thr Lys Asn Gly Glu Gin Thr Gin 145 150 155 160 Thr Ala Arg Asp Val Gin Asn Leu Ile Gin Ser Ile Ser Gly Ser Gly 165 170 175 Tyr Gly Asn Met Gin Ser Leu Ala Gly Glu Leu Ser Gly Arg Ala Trp 180 185 190 Gly Glu Met Leu Cys Lys Met Val Asn Asp Ser Asn Tyr Glu Ser Glu 195 200 205 Gin Ala Leu Leu Ala Thr Gly Asn Asn Pro Glu Glu Gin Lys Arg Arg 210 215 220 Phe Leu Leu Arg Val Lys Lys Lys Val Asn Asp Asn Lys Gin Leu Lys 225 230 235 240 Asp Lys Leu Asp Pro Phe Leu Lys Arg Leu Asp Val Leu Gin Thr Glu 245 250 255 Phe Gly Val Thr Asp Pro Thr Ala Asn His Asn Lys Gin Gly Ile His 260 265 270 Tyr Cys Thr Glu Asn Lys Glu Thr Gly Lys Cys Asp Pro Ile Lys Asn 275 280 285 Val Phe Arg Thr Thr Arg Leu Asp Asn Glu Leu Glu Gin Glu Ile Gin 290 295 300 Thr Leu Thr Leu Asp Leu Ile Lys Ala Ser Asn Lys Asp Ala Gin Ser 305 310 315 320 Gin Ala Tyr Ala Asn Phe Asn Gin Arg Ile Lys Leu Leu Thr Leu Lys 325 330 335 Tyr Leu Lys Glu Ile Thr Asn Gin Met Leu Phe Leu Asn Gin Thr Met 340 345 350 Ala Met Gin Ser Glu Ile Met Thr Asp Asp Tyr Phe Arg Gin Asn Asn 355 360 365 Asp Gly Phe Gly Glu Lys Glu Asn His Ile Asp Lys Gin Leu Thr Gin 370 375 380 Lys Arg Ile Asn Glu Arg Glu Arg Ala Arg Ile Tyr Phe Gin Asn Pro 385 390 395 400 Asn Val Lys Phe Asp Gin Phe Gly Phe Pro Ile Phe Ser Ile Trp Asp 405 410 415 WO 98/18323 PCT/US97/19575 -168- INFORMATION FOR SEQ ID NO:96: SEQUENCE CHARACTERISTICS: LENGTH: 376 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...376 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96: Val Asn Lys Trp Ile Lys Gly Ala Val Val Phe Val Gly Gly Phe Ala 1 5 10 Thr Ile Thr Thr Phe Ser Leu Ile Tyr His Gin Lys Pro Lys Ala Pro 20 25 Leu Asn Asn Gin Pro Ser Leu Leu Asn Asp Asp Glu Val Lys Tyr Pro 40 Leu Gin Asp Tyr Thr Phe Thr Gln Asn Pro Gin Pro Thr Asn Thr Glu 55 Ser Ser Lys Asp Ala Thr Ile Lys Ala Leu Gin Glu Gin Leu Lys Ala 70 75 Ala Leu Lys Ala Leu Asn Ser Lys Glu Met Asn Tyr Ser Lys Glu Glu 90 Thr Phe Thr Ser Pro Pro Met Asp Pro Lys Thr Thr Pro Pro Lys Lys 100 105 110 Asp Phe Ser Pro Lys Gin Leu Asp Leu Leu Ala Ser Arg Ile Thr Pro 115 120 125 Phe Lys Gin Ser Pro Lys Asn Tyr Glu Glu Asn Leu Ile Phe Pro Val 130 135 140 Asp Asn Pro Asn Gly Ile Asp Ser Phe Thr Asn Leu Lys Glu Lys Asp 145 150 155 160 Ile Ala Thr Asn Glu Asn Lys Leu Leu Arg Thr Ile Thr Ala Asp Lys 165 170 175 Met Ile Pro Ala Phe Leu Ile Thr Pro Ile Ser Ser Gin Ile Ala Gly 180 185 190 Lys Val Ile Ala Gin Val Glu Ser Asp Ile Phe Ala Ser Met Gly Lys 195 200 205 Ala Val Leu Ile Pro Lys Gly Ser Lys Val Ile Gly Tyr Tyr Ser Asn 210 215 220 Asn Asn Lys Met Gly Glu Tyr Arg Leu Asp Ile Val Trp Ser Arg Ile 225 230 235 240 Ile Thr Pro His Gly Ile Asn Ile Met Leu Thr Asn Ala Lys Gly Ala 245 250 255 Asp Ile Lys Gly Tyr Asn Gly Leu Val Gly Glu Leu Ile Glu Arg Asn 260 265 270 WO 98/18323 PCT/US97/19575 -169- Phe Gin Arg Tyr Gly Val Pro Leu Leu Leu Ser Thr Leu Thr Asn Gly 275 280 285 Leu Leu Ile Gly Ile Thr Ser Ala Leu Asn Asn Arg Gly Asn Lys Glu 290 295 300 Glu Val Thr Asn Phe Phe Gly Asp Tyr Leu Leu Leu Gin Leu Met Arg 305 310 315 320 Gin Ser Gly Met Gly Ile Asn Gin Val Val Asn Gin Ile Leu Arg Asp 325 330 335 Lys Ser Lys Ile Ala Pro Ile Val Val Ile Arg Glu Gly Ser Arg Val 340 345 350 Phe Ile Ser Pro Asn Thr Asp Ile Phe Phe Pro Ile Pro Arg Glu Asn 355 360 365 Glu Val Ile Ala Glu Phe Leu Lys 370 375 INFORMATION FOR SEQ ID NO:97: SEQUENCE CHARACTERISTICS: LENGTH: 916 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...916 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97: Val Asp Leu Arg Ile Gin Ser Lys Glu Val Ser His Asn Leu Lys Glu 1 5 10 Leu Ser Lys Thr Leu Ile Ser Tyr Pro Phe Glu Lys His Val Glu Ala 25 Leu Gly Glu Gin Cys Ser Asn Phe Val Ser Ile Pro Ile Asn Asn Asp 40 Asp Tyr Ser Asn Ile Cys Thr Phe Val Ser Asp Phe Ile Asn Leu Ile 55 Ala Ser Tyr Asn Leu Leu Glu Ser Phe Leu Asp Phe Tyr Lys Asp Lys 65 70 75 so Leu Lys Leu Ser Glu Leu Val Thr Glu Tyr Ala Asn Val Thr Asn Asn 90 Leu Leu Phe Lys Lys Leu Ile Lys His Leu Ser Gly Asn Asn Gin Leu 100 105 110 Val Lys Asn Phe Tyr Gin Cys Ile Arg Glu Ile Ile Lys Tyr Asn Ala 115 120 125 Pro Asn Lys Glu Tyr Lys Pro Asn Gin Phe Phe Ile Ile Gly Lys Gly 130 135 140 Lys Gin Lys Gin Leu Ala Lys Ile Tyr Ser His Leu Lys Glu Leu Ser 145 150 155 160 1* WO-98/18323 PCTIUS97/19575 170 Ala Giu Pro Pro Ile 225 Ser Glu Gin Lys Leu 305 Giu Giu Lys Giu Phe 385 Val Leu Gly Pro Lys 465 Asn Lys Lys Thr Asn 545 Leu Ile His Ser Giu Lys Ile 210 Glu Leu Giu Ile Asp 290 Leu Pro Ser Phe Phe 370 His Pro Giu His Asn 450 Phe Ile Ile His Ser 530 Met Leu Arg Giu Giu Leu Thr 195 Asn Lys Ile Giu Cys 275 Ile Val Ile Gly Giu 355 Al a Leu Ile Ala Trp 435 Lys Asp Ser Lys Asp 515 Phe Gin Ala Vai Ile Ile Asp 180 Giu Giu His Arg Pro 260 Lys Lys Asn Gin Ile 340 Ala Giu Asn Met Ile 420 Phe Ile Lys Lys Gin 500 Asn Leu Leu Ile Arg 580 Lys Lys 165 Lys Ile Asn Asp Giu 245 Giu Asn Ser Ser Arg 325 Tyr Asn Tyr Ile Lys 405 Ser Phe Trp Asp Lys 485 Ser Asn Phe Lys Val1 565 His Leu Pro Ile Lys Phe Glu 230 Ile Tyr Tyr Met Giu 310 Ser Leu Lys Cys Asn 390 Giu Thr Gin Ile Leu 470 Tyr Lys Asp Ala Ile 550 Gin Asn Glu Gln Phe Asp Lys 215 Ile Giu Lys Ile Met 295 Ile Leu Phe Giu Arg 375 Asn Tyr Lys Leu Pro 455 Giu Leu Asp I le Lys 535 Asp Asp Asn Val Asp Lys Ile 200 Arg Lys Asn Ile Giu 280 Cys Val Trp Pro Lys 360 Giu Gly Lys Glu Ser 440 Leu Ile Gln Phe Leu 520 Gly Ser Ser Lys Tyr Met Thr 185 Ile Gin Lys His Asn 265 Ser Gin Arg Giu Lys 345 Phe Cys Leu Giu Thr 425 Leu Giu Tyr Giu Phe 505 Gin Ser Leu Pro Leu 585 Asp Giu 170 Thr Lys Phe Asp Cys 250 Asp His Phe Tyr Ser 330 Asn Lys Asn Ser Pro 410 Gly Phe Phe Phe Ile 490 Ser Leu Phe Ile Gin 570 Pro Cys Ile Phe Ile Giu 220 Glu Asn Leu Val Leu 300 Tyr Lys Gly Ser Tyr 380 Gin Ile Ala Lys Lys 460 Ser Gln Gin Phe Giu 540 Lys Ser Giu Lys Leu Thr Asp 205 Phe Arg Giu Lys Asn 285 Lys Ser Ile Giu Lys 365 Thr Phe Thr Ser Thr 445 Arg His Giu Lys Phe 525 Ile Giu Tyr Lys Ser Lys Lys 190 Giu Giu Asn Cys Asn 270 Asp Gin Asn Leu Ile 350 Asn Ala Giu Asp Gin 430 Asn Ser Giu Ser Ile 510 Giu Leu Phe Gin Tyr 590 His Lys 175 Phe Lys Ser Lys Asn 255 Ile Val1 Ile Leu Asp 335 Lys Val Phe Lys Asn 415 Leu Phe Lys Ser Leu 495 Glu Asn Giu Asn Leu 575 Thr Asp Leu Thr Tyr Asn Glu.

240 Ser Gin Ser Asp Phe 320 Asn Asp Ser Asn Phe 400 Asp Ser Asn Ile Phe 480 Lys Ser Asp Tyr Lys 560 Lys Giu His WO 98/18323 PCT/US97/19575 171 595 600 605 Asn Glu Pro Ile Ile Leu Ser Gin Gin Ser Thr Gly Phe Gin Trp Ala 610 615 620 Phe Asn Phe Met Phe Gly Phe Leu Tyr Asn Val Gly Ser His Phe Ser 625 630 635 640 SPhe Asn His Asn Ile Ile Tyr Val Met Asp Glu Pro Ala Thr His Leu 645 650 655 Ser Val Pro Ala Arg Lys Glu Phe Arg Lys Phe Leu Lys Glu Tyr Ala 660 665 670 His Lys Asn His Val Thr Phe Val Leu Ala Thr His Asp Pro Phe Leu 675 680 685 Val Asp Thr Asp His Leu Asp Glu Ile Arg Ile Val Glu Lys Glu Thr 690 695 700 Glu Gly Ser Val Ile Lys Asn His Phe Asn Tyr Pro Leu Asn Asn Ala 705 710 715 720 Ser Lys Asp Ser Asp Ala Leu Asp Lys Ile Lys Arg Ser Leu Gly Val 725 730 735 Gly Gin His Val Phe His Asn Pro Gin Lys His Arg Ile Ile Phe Val 740 745 750 Glu Gly Ile Thr Asp Tyr Cys Tyr Leu Ser Ala Phe Lys Leu Tyr Leu 755 760 765 Arg Tyr Lys Glu Tyr Lys Asp Asn Pro Ile Pro Phe Thr Phe Leu Pro 770 775 780 Ile Ser Gly Leu Lys Asn Asp Ser Asn Asp Met Lys Glu Thr Ile Glu 785 790 795 800 Lys Leu Cys Glu Leu Asp Asn His Pro Ile Val Leu Thr Asp Asp Asp 805 810 815 Arg Lys Cys Val Phe Asn Gin Gin Ala Thr Ser Glu Arg Phe Lys Arg 820 825 830 Ala Asn Glu Glu Met His Asp Pro Ile Thr Ile Leu Gin Leu Ser Asp 835 840 845 Cys Asp Arg His Phe Lys Gin Ile Glu Asp Cys Phe Ser Ala Asn Asp 850 855 860 Arg Asn Lys Tyr Ala Lys Asn Lys Gin Met Glu Leu Ser Met Ala Phe 865 870 875 880 Lys Thr Arg Leu Leu Tyr Gly Gly Glu Asp Ala Ile Glu Lys Gin Thr 885 890 895 Lys Arg Asn Phe Leu Lys Leu Phe Lys Trp Ile Ala Trp Ala Thr Asn 900 905 910 Leu Ile Lys Asn 915 INFORMATION FOR SEQ ID NO:98: SEQUENCE CHARACTERISTICS: LENGTH: 176 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 WO 9818323PCTIUS97/19575 172- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 .176 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98: Met Thr Ala Met Met Arg Tyr Phe His Ile Tyr Ala 1 Phe Lys Lys Lys Arg Thr Gly Ala Ala 145 Val Pro Ala Ser 50 Giu Gly Lys Ala Leu 130 Phe Leu Ala Gin Lys His Leu Thr 1.00 Ile Gly Met Gly Leu Asp Lys Ile Val1 Gin Met Ile Val1 Ser 165 Leu Thr Glu Ala 70 Ile Thr Leu Phe Al a 150 Val Phe Gly Giu 55 Met Gly Lys His Cys 135 Phe Val Ala Ala Arg Pro Thr Ile Lys 120 Val Lys Phe Val 25 Lys Leu Lys Pro Lys 105 Ala Phe Asp Phe Gly Lys Phe Ile 75 Tyr Ile Val Leu Lys 155 Ala Leu Glu Leu Glu Giu Giu Gly Leu 140 Arg Ile Thr Ser Trp Lys Pro Ile Arg Ile 125 Phe Met Tyr Thr Leu 30 Val Gly Arg Asn Gly 110 Val Tyr Phe Trp Phe 15u Leu Phe Glu Leu Phe Phe Leu Ile Ser 175 Phe Phe Giu Ile Tyr Glu Leu Gin Ser Ser 160 Leu INFORMATION FOR SEQ ID NO:99: SEQUENCE CHARACTERISTICS: LENGTH: 222 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. 222 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 99: Met Phe Lys Asn Ala Leu Asn Ile Gln Asp Phe Ser Phe Lys Asn His 1 5 10 Thr Ser Thr Ala Ile Ile Gly Thr Asn Gly Ala Gly Lys Ser Thr Leu 25 Ile Asn Thr Ile Leu Gly Ile Arg Ser Asp Tyr Asn Phe Lys Ala Gln WO. 98/18323 PCT/US97/19575 173- 40 Asn Asn Asn Ile Pro Tyr His Asp Asn Val Ile Pro Gin Arg Lys Gin 55 Leu Gly Val Val Ser Asn Leu Phe Asn Tyr Pro Pro Gly Leu Asn Ala 65 70 75 Asn Asp Leu Phe Lys Phe Tyr Gin Phe Phe His Lys Asn Cys Thr Leu 90 Asp Leu Phe Glu Lys Asn Leu Leu Asn Lys Thr Tyr Glu His Leu Ser 100 105 110 Asp Gly Gin Lys Gin Arg Leu Lys Ile Asp Leu Ala Leu Ser His His 115 120 125 Pro Gin Leu Val Ile Met Asp Glu Pro Glu Thr Ser Leu Glu Gin Asn 130 135 140 Ala Leu Ile Arg Leu Ser Asn Leu Ile Ser Leu Arg Asn Thr Gin Gin 145 150 155 160 Leu Thr Ser Ile Ile Ala Thr His Asp Pro Ile Val Leu Asp Ser Cys 165 170 175 Glu Trp Val Leu Leu Leu Lys Asn Gly Asn Ile Ala Gin Tyr Lys Pro 180 185 190 Leu Asn Ser Ile Leu Lys Ser Val Ala Lys Thr Phe Asn Phe Lys Glu 195 200 205 Lys Pro Thr Thr Lys Asp Leu Leu Ala Leu Leu Lys Asp Ile 210 215 220 INFORMATION FOR SEQ ID NO:100: SEQUENCE CHARACTERISTICS: LENGTH: 406 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...406 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100: Met Tyr Ala Ala His Pro Ile Lys Pro Ile Lys Ala Pro Lys Leu Lys 1 5 10 Ser Gin Phe Leu Arg Arg Val Phe Val Gly Ala Ser Ile Arg Arg Trp 25 Asn Asp Gin Ala Cys Pro Leu Glu Phe Val Glu Leu Asp Lys Gin Ala 35 40 His Lys Ala Met Ile Ala Tyr Leu Leu Ala Lys Asp Leu Lys Asp Arg 55 Gly Lys Asp Leu Asp Leu Asp Leu Leu Ile Lys Tyr Phe Cys Phe Glu 70 75 Phe Leu Glu Arg Leu Val Leu Thr Asp Ile Lys Pro Pro Ile Phe Tyr

SV

WO 98/18323 PCT/US97/19575 174- Ala Ser Glu Ser 145 Phe Lys Lys Gin Gly 225 Leu Phe Lys Lys Glu 305 Asp Thr Lys Ser Leu 385 Leu Leu Leu Tyr 130 Ala Asn Gin Glu Lys 210 His Lys His Gin Glu 290 Asp Lys Leu Val His 370 Glu Phe Gin Gin 115 Leu His Pro Leu Asp 195 Arg Thr Ala Asp Ser 275 Met Leu Ser Tyr Cys 355 Gly Leu Arg Gin 100 Asp Ser Phe Asn His 180 Leu Trp Leu Cys Leu 260 Val Gin Lys His Asn 340 Asp Ile Arg Asp Thr Glu His Tyr Met 165 Asn Lys Ser Cys Lys 245 Pro Ala Asn Tyr Gin 325 Ser His Ser Ser Phe 405 His Ile Arg Ala 150 Tyr Asn Lys Gin Val 230 Ser Glu Gly Lys Phe 310 Ile Asp Leu Ser Gin 390 Lys Ser Ser Pro 135 Ser Gly Asp Leu Thr 215 Ala Met Ile Leu Val 295 Thr Val Glu Ser Tyr 375 Thr Lys Ala 120 Gin Lys Val His Val 200 Pro Ile Arg Leu Asp 280 Tyr Glu Phe Tyr Ala 360 Asp Glu Glu 105 Tyr Ile Trp Lys Leu 185 Ser Arg Met Ile Thr 265 His Ser Asn Thr Leu 345 Phe Leu Leu 90 Leu Phe Leu Glu Glu 170 Phe Met Val Gly Asn 250 Arg Cys Phe Glu Lys 330 Gly Leu Ile Leu Ala Ser Glu Phe 155 Ile Glu Phe Pro Tyr 235 His Asp Ile Val Phe 315 Asp Val Glu Gin Asp 395 Ser Leu Thr 140 Asp Lys Gly Gly Gin 220 Leu Phe Ile Lys Ser 300 Lys Ala Cys Ala Gly 380 Leu Tyr Glu 125 Gin Ile Asp Leu Gin 205 Thr Leu Leu Ile Glu 285 Leu Asn Glu Gly Gin 365 Ala Asp Val 110 Glu Ile Ile Lys Phe 190 Leu Ser Ser Gly Thr 270 Ile Gly Arg Glu Glu 350 Ile Lys Leu Ala Leu Leu Tyr Ile 175 Gly Arg Val Phe Gly 255 Pro Glu Val Tyr Leu 335 Leu Ser Asn Gly Gln Lys Glu His 160 Asp Glu Phe Leu Asp 240 Leu Ile Lys Gin Lys 320 Phe Leu Leu Leu Lys 400 INFORMATION FOR SEQ ID NO:101: SEQUENCE CHARACTERISTICS: LENGTH: 335 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 WO 9818323PCTIUS97/19575 175- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .335 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l0i: Vai Leu Trp Val Leu Tyr Phe Leu Thr Ser Leu Phe 1 Ile Lys Gly Met Leu Arg Pro Ile Ile 145 Ile Leu Gly Cys Phe 225 Ser Asn Phe Leu Leu 305 Ala Val Ile Ile 50 Pro Ser Leu Leu Ala 130 Asn.

Ala Leu Lys Gly 210 Phe Ile Leu Asn Pro 290 Ile Tyr Leu Gin Phe Phe Gly Ile Val 115 Phe Ile Leu Ala Ile 195 Ile Gly Leu His Tyr 275 Phe Val Leu Trp Giy Leu Lys Phe Leu 100 Val Leu Ile Leu Tyr 180 Phe Ser Leu Arg Leu 260 Pro Ile Ile Asn Lys His Phe Pro 70 Giu Ala Asp Ala Gly 150 Ile Val Gly Leu Leu 230 Lys Thr Pro Ile Leu 310 Gin Lys His Al a 55 Phe Asp Val Phe Ile 135 Phe His Leu Asp His 215 Met Ile Leu Leu Ser 295 Val1 Val Met 25 Arg Ala Phe Asn Val 105 Pro Met Gly Ile Phe 185 Gly Ser Tyr Arg Phe 265 Ala Leu Ile Ala Phe Pro Tyr Gly 75 Ser Cys Phe Vai Ala 155 Pro Val Tyr Giu Val 235 Lys Phe Ile Arg Cys 315 Glu Val1 Arg Leu Leu Leu Ile Ser Gly 140 Ser Ser Leu Phe Gin 220 Ile Ala Leu Leu Leu 300 Tyr Lys Ile Asp Aia Giu Ser Ser Ile Leu 125 Ile Gly Ser Asn Leu 205 Lys Giu Thr Gin Ile 285 Asp Leu Arg Cys Asn Gly Pro Leu Pro Ser 110 Pro Ser Ile Leu Phe 190 Gly Ile Val1 Met Gin 270 Leu Al a Ile Ala Ser Ala Gly Phe Val Lys Ser Tyr Asn.

Cys Ser 175 Pro Leu Ser Leu Pro 255 Arg Cys Tyr Gly Phe 335 Leu Asn Leu Giu Phe Ile Thr Phe Ala Ala 160 Cys Ser Val Val1 Phe 240 Asp Ser Asn Ala Tyr 320 INFORMATION FOR SEQ ID NO:102: SEQUENCE CHARACTERISTICS: LENGTH. 96 amino acids TYPE: amino acid WO 98/18323 PCT/US97/19575 176- TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...96 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: Met Lys Lys Val Ile Val Ala Leu Gly Val Leu Ala Phe Ala Asn Val 1 5 10 Leu Met Ala Thr Asp Val Lys Ala Leu Val Lys Gly Cys Ala Ala Cys 25 His Gly Val Lys Phe Glu Lys Lys Ala Leu Gly Lys Ser Lys Ile Val 40 Asn Met Met Ser Glu Lys Glu Ile Glu Glu Asp Leu Met Ala Phe Lys 55 Ser Gly Ala Asn Lys Asn Pro Val Met Thr Ala Gin Ala Lys Lys Leu 65 70 75 Ser Asp Glu Asp Ile Lys Ala Leu Ala Lys Tyr Ile Pro Thr Leu Lys 90 INFORMATION FOR SEQ ID NO:103: SEQUENCE CHARACTERISTICS: LENGTH: 156 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...156 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103: Met Arg Asp Phe Asn Asn Ile Gin Ile Thr Arg Leu Lys Val Arg Gin 1 5 10 Asn Ala Val Phe Glu Lys Leu Asp Leu Glu Phe Lys Asp Gly Leu Ser 25 Ala Ile Ser Gly Ala Ser Gly Val Gly Lys Ser Val Leu Ile Ala Ser 40 Leu Leu Gly Ala Phe Gly Leu Lys Glu Ser Asn Ala Ser Asn Ile Glu WO 98/18323 PCT/US97/19575 -177- 55 Val Glu Leu Ile Ala Pro Phe Leu Asp Thr Glu Glu 70 75 Arg Glu Asp Glu His Glu Pro Leu Val Ile Ser Val 85 90 Lys Thr Arg Tyr Phe Leu Asn Gin Thr Ser Leu Ser 100 105 Lys Ala Leu Leu Lys Gly Leu Ile Lys Arg Leu Ser 115 120 Ser Gin Asn Glu Leu Asn Asp Ile Leu Met Leu Ser 130 135 140 Tyr Ile Gin Asn Lys Asn Arg Arg Leu Ala Pro Phe 145 150 155 INFORMATION FOR SEQ ID NO:104: SEQUENCE CHARACTERISTICS: LENGTH: 118 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...118 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104: Tyr Gly Ile Phe Ile Lys Lys Glu Lys Asn Thr Leu 110 Asn Asp Arg Phe 125 Leu Leu Asp Gly Val Met Leu Met Ala Ile Phe Thr Pro Tyr Ile Leu Ile Leu Lys Met 1 Met Phe Glu Met Lys Gly Thr Lys Cys Val Glu Glu Asn Tyr Lys Asn Gly Asn Gin Asp Phe 115 Ser Arg Leu His Val Thr 100 His 5 Met Asp Asp Leu Asp Lys Arg Ser Ile Ser Ile 70 Ile Lys Ser Leu Lys Asn Gly Arg Phe Ala 25 Leu Arg Phe Phe Phe 105 Met Asp Asn Gin Asp Ile Glu Phe Arg Leu Gin Lys 110 Gin Gly Lys Asn Ala Glu INFORMATION FOR SEQ ID NO:105: SEQUENCE CHARACTERISTICS: LENGTH: 355 amino acids WO 98/18323 PCT/US97/19575 178- TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...355 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105: Met Asn Ile Lys Ile Leu Lys Ile Leu Val Gly Gly Leu Phe Phe Leu 1 5 10 Ser Leu Asn Ala His Leu Trp Gly Lys Gin Asp Asn Ser Phe Leu Gly 20 25 Ile Gly Glu Arg Ala Tyr Lys Ser Gly Asn Tyr Ser Lys Ala Ala Ser 40 Tyr Phe Lys Lys Ala Cys Asn Asp Gly Val Ser Glu Gly Cys Thr Gin 55 Leu Gly Ile Ile Tyr Glu Asn Gly Gin Gly Thr Arg Ile Asp Tyr Lys 70 75 Lys Ala Leu Glu Tyr Tyr Lys Thr Ala Cys Gin Ala Asp Asp Arg Glu 90 Gly Cys Phe Gly Leu Gly Gly Leu Tyr Asp Glu Gly Leu Gly Thr Ala 100 105 110 Gin Asn Tyr Gin Glu Ala Ile Asp Ala Tyr Ala Lys Ala Cys Val Leu 115 120 125 Lys His Pro Glu Ser Cys Tyr Asn Leu Gly Ile Ile Tyr Asp Arg Lys 130 135 140 Ile Lys Gly Asn Ala Ala Gin Ala Val Thr Tyr Tyr Gin Lys Ser Cys 145 150 155 160 Asn Phe Asp Met Ala Lys Gly Cys Tyr Ile Leu Gly Thr Ala Tyr Glu 165 170 175 Lys Gly Phe Leu Glu Val Lys Gin Ser Asn His Lys Ala Val Ile Tyr 180 185 190 Tyr Leu Lys Ala Cys Arg Leu Asn Glu Gly Gin Ala Cys Arg Ala Leu 195 200 205 Gly Ser Leu Phe Glu Asn Gly Asp Ala Gly Leu Asp Glu Asp Phe Glu 210 215 220 Val Ala Phe Asp Tyr Leu Gin Lys Ala Cys Ala Leu Asn Asn Ser Gly 225 230 235 240 Gly Cys Ala Ser Leu Gly Ser Met Tyr Met Leu Gly Arg Tyr Val Lys 245 250 255 Lys Asp Pro Gin Lys Ala Phe Asn Tyr Phe Lys Gin Ala Cys Asp Met 260 265 270 Gly Ser Ala Val Ser Cys Ser Arg Met Gly Phe Met Tyr Ser Gin Gly 275 280 285 Asp Thr Val Ser Lys Asp Leu Arg Lys Ala Leu Asp Asn Tyr Glu Arg 290 295 300 Gly Cys Asp Met Gly Asp Glu Val Gly Cys Phe Ala Leu Ala Gly Met WO 98/18323 PCT/US97/19575 -179- 305 310 315 320 Tyr Tyr Asn Met Lys Asp Lys Glu Asn Ala Ile Met Ile Tyr Asp Lys 325 330 335 Gly Cys Lys Leu Gly Met Lys Gin Ala Cys Glu Asn Leu Thr Lys Leu 340 345 350 Arg Gly Tyr 355 INFORMATION FOR SEQ ID NO:106: SEQUENCE CHARACTERISTICS: LENGTH: 193 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...193 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106: Met Lys Glu Lys Asn Phe Trp Pro Leu Gly Ile Met Ser Val Leu Ile 1 5 10 Phe Gly Leu Gly Ile Val Val Phe Leu Val Val Phe Ala Leu Lys Asn 25 Ser Pro Lys Asn Asp Leu Val Tyr Phe Lys Gly His Asn Glu Val Asp 40 Leu Asn Phe Asn Ala Met Leu Lys Thr Tyr Glu Asn Phe Lys Ser Asn 55 Tyr Arg Phe Ser Val Gly Leu Lys Pro Leu Thr Glu Ser Pro Lys Thr 70 75 Pro Ile Leu Pro Tyr Phe Ser Lys Gly Thr His Gly Asp Lys Lys Ile 85 90 Gin Glu Asn Leu Leu Asn Asn Ala Leu Ile Leu Glu Lys Ser Asn Thr 100 105 110 Leu Tyr Ala Gin Leu Gin Pro Leu Lys Pro Ala Leu Asp Ser Pro Asn 115 120 125 Ile Gin Val Tyr Leu Ala Phe Tyr Pro Ser Gin Ser Gin Pro Arg Leu 130 135 140 Leu Gly Thr Leu Asp Cys Lys Asn Ala Cys Glu Pro Leu Lys Phe Asp 145 150 155 160 Leu Leu Glu Gly Asp Lys Val Gly Arg Tyr Lys Ile Leu Phe Lys Phe 165 170 175 Val Phe Lys Asn Lys Glu Glu Leu Ile Leu Glu Gin Leu Ala Phe Phe 180 185 190 Lys WO 98/18323 PCT/US97/19575 -180- INFORMATION FOR SEQ ID NO:107: SEQUENCE CHARACTERISTICS: LENGTH: 289 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...289 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107: Leu Gly Ile Asn Met Cys Ser Lys Lys Ile Arg Asn Leu Ile Leu Cys 1 5 10 Phe Gly Phe Ile Leu Ser Leu Cys Ala Glu Glu Asn Ile Thr Lys Glu 25 Asn Met Thr Glu Thr Asn Thr Thr Glu Glu Asn Thr Pro Lys Asp Ala 40 Pro Ile Leu Leu Glu Glu Lys Arg Ala Gin Thr Leu Glu Leu Lys Glu 55 Glu Asn Glu Val Ala Lys Lys Ile Asp Glu Lys Ser Leu Leu Glu Glu 65 70 75 Ile His Lys Lys Lys Arg Gin Leu Tyr Met Leu Lys Gly Glu Leu His 90 Glu Lys Asn Glu Ser Ile Leu Phe Gin Gin Met Ala Lys Asn Lys Ser 100 105 110 Gly Phe Phe Ile Gly Val Ile Leu Gly Asp Ile Gly Ile Asn Ala Asn 115 120 125 Pro Tyr Glu Lys Phe Glu Leu Leu Ser Asn Ile Gin Ala Ser Pro Leu 130 135 140 Leu Tyr Gly Leu Arg Ser Gly Tyr Gin Lys Tyr Phe Ala Asn Gly Ile 145 150 155 160 Ser Ala Leu Arg Phe Tyr Gly Glu Tyr Leu Gly Gly Ala Met Lys Gly 165 170 175 Phe Lys Ser Asp Ser Leu Ala Ser Tyr Gin Thr Ala Ser Leu Asn Ile 180 185 190 Asp Leu Leu Met Asp Lys Pro Ile Asp Lys Glu Lys Arg Phe Ala Leu 195 200 205 Gly Ile Phe Gly Gly Val Gly Val Gly Trp Asn Gly Met Tyr Gin Asn 210 215 220 Leu Lys Glu Ile Arg Gly Tyr Ser Gin Pro Asn Ala Phe Gly Leu Val 225 230 235 240 Leu Asn Leu Gly Val Ser Met Thr Leu Asn Leu Lys His Arg Phe Glu 245 250 255 Leu Ala Leu Lys Met Pro Pro Leu Lys Glu Thr Ser Gin Thr Phe Leu 260 265 270 Tyr Tyr Phe Lys Ser Thr Asn Ile Tyr Tyr Ile Ser Tyr Asn Tyr Leu WO 98/18323 WO 9818323PCTIUS97/19575 181 Leu INFORMATION FOR SEQ ID NO:108: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 668 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc-feature LOCATION 668 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i08: Met Arg Lys Leu Phe Ile Pro Leu Leu Leu Phe Sen 1 Asn Leu Thr Ala ser Thr Phe Ile Leu 145 Lys Val Ser Gly Glu Giu Glu Tyr Ala Ser Ile Thr Pro 130 Lys Phe Phe Asn Asn 210 Glu Lys Gly 35 Ala Asn Leu Glu Asp 115 Lys Giu Giu Glu Glu 195 Thr Phe Asn Thr Thr Leu Ser Asn 100 Ala His Ala Ala Thr 180 Asn Lys Thr 5 Gly Gin Tyr Phe Pro Phe Gin Ser Phe Thr 165 Leu Pro Asn Asn Phe Thr Asn Thr 70 Val1 Leu Gly Lys Asp 150 Ser Asn Asn Asp Leu Ile Giu 40 Leu Ala Val1 Tyr Thr 120 Vai Ile Ser Ile Phe 200 Trp, Leu Giu 25 Lys Pro Glu Leu Asn 105 Ile Leu Asp Ile Lys 185 Asn Gin Asn Gly His Asp Ile 75 Met Asn Leu Gly Tyr 155 Asp Asn Cys Phe Ile Phe Thr Thr Sen Tyr Asn Gly Glu 140 Thr Thr Leu Pro Thr 220 Ala Ala Glu Thr Ile Lys Asn Val Val 125 Ala Leu Asn Ile Tyr 205 Pro Val Leu Thr Thr Leu Leu Gly Lys 110 Ile Phe Phe Thr Met 190 Asn Gin Leu Giu Giy Lys Lys Lys Gin Leu Giu Asp Leu Gin 175 Lys Asn Thr Asp Al a Leu Asn Arg Phe Leu Ser Thr Ser Pro 160 Arg Tyr Asn Al a Ser 225 230 235 240 Gin Ser Trp Gly Asp Ala Ile Leu Asn Ala Pro Phe Giu Phe Thr Asn I' f WO 98/18323 PCT/US97/19575 182- Ser Val Lys Val 305 Asn Pro Leu Asn Val 385 Tyr Ser Gly Asn Asn 465 Ser Phe Ala Tyr Val 545 Ile Arg Tyr Asp Val 625 Ser His Ser Asn Gin 290 Val Asp Lys Arg Gly 370 Glu Asn Asn Phe Ala 450 Leu Thr Ser Lys Tyr 530 Gin Thr Asn Asn Val 610 Gly Gly Phe Thr Gly 275 Gly Leu Gly Lys Thr 355 Asn Lys Val Tyr Leu 435 Leu Asn Ile Asn Ile 515 Gly Gin Thr Phe Ser 595 Ala Ile Gly Lys Asp 260 Arg Ile Lys Glu Leu 340 Ile Met Asp Cys Pro 420 Gly Pro Ala Gin Ala 500 Gly Ile Leu Tyr Ser 580 Tyr Thr Ser Asp Val 660 245 Cys Val Ile Asn Tyr 325 Phe Leu Thr Ser Ser 405 Asn Val Ile Ser Lys 485 Ser Tyr Ile Ser Ser 565 Ser Tyr Gly Ile Tyr 645 Phe Asp Asp Asn Ser 310 Gly Gly His Tyr Asn 390 Leu Ser Thr Asn Leu 470 Thr Gin Gin Lys Tyr 550 Asn Ser Val Leu Pro 630 Thr Phe Asp Lys 280 Phe Val Leu Asp Phe 360 Arg Lys Gly Tyr Ala 440 Ala Thr Val Phe Tyr 520 Asn Gly Asn Gly Asn 600 Tyr Ile Ser Tyr Pro 265 Val Arg .Val Gly Leu 345 Ser Val Pro Gly His 425 Val Asn Gin Thr Arg 505 Phe Tyr Gly Ser Ile 585 Lys Arg Gin Phe Gly 665 250 Ser Asp Lys Gly Val 330 Lys His Pro Lys Ser 410 Asn Trp Leu Asp Ser 490 Ser Asn Ala Ile Pro 570 Phe Val Tyr Arg Val 650 Trp Lys Gin Lys Leu 315 Glu Thr Thr Val Asp 395 Asn Cys Gin Gly Leu 475 Ser Pro Asp Lys Asp 555 Thr Gly Lys Lys Lys 635 Phe Val Cys Gin Ile 300 Ala Ala Ile Lys Thr 380 Ser Gin Ala Gin Ser 460 Ala Val Ile Phe Ala 540 Leu Gly Gly Gly His 620 Ala Asn Phe Val Tyr 285 Glu Asn Tyr Asn Gly 365 Lys Asp Pro Asp Leu 445 Gin Asn Thr Leu Ile 525 Val Leu Ile Leu Ser 605 Ser Ser Glu Asn 270 Ile Ile Gly Ala Leu 350 Tyr Asp Gly Ala Val 430 Ile Thr Ser Asn Gly 510 Gly Asn Leu Gin Arg 590 Gly Lys Val Gly 255 Pro Leu Asp Tyr Leu 335 Glu Gly Gly Leu Phe 415 Pro Asn Asn Met His 495 Val Leu Gin Asp Thr 575 Gly Asn Tyr Val Ala 655 Gly Asn Ala Gly 320 Asp Asp His Gin Pro 400 Pro Ala Gin Tyr Leu 480 His Asn Ala Lys Phe 560 Lys Leu Leu Ser Ser 640 Ser INFORMATION FOR SEQ ID NO:109: WO 98/18323 PCT/US97/19575 -183 SEQUENCE CHARACTERISTICS: LENGTH: 63 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...63 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109: Met Asn Thr Glu Ile Leu Thr Ile Met Leu Val Val Ser Val Leu Met 1 5 10 Gly Leu Val Gly Leu Ile Ala Phe Leu Trp Gly Val Lys Ser Gly Gin 25 Phe Asp Asp Glu Lys Arg Met Leu Glu Ser Val Leu Tyr Asp Ser Ala 35 40 Ser Asp Leu Asn Glu Ala Ile Leu Gin Glu Lys Arg Gin Lys Asn 55 INFORMATION FOR SEQ ID NO:110: SEQUENCE CHARACTERISTICS: LENGTH: 406 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...406 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110: Met Val Phe Phe His Lys Lys Ile Ile Leu Asn Phe Ile Tyr Ser Leu 1 s 10 is Met Val Ala Phe Leu Phe His Leu Ser Tyr Gly Val Leu Leu Lys Ala 25 Asp Gly Met Ala Lys Lys Gln Thr Leu Leu Val Gly Glu Arg Leu Val 40 Trp Asp Lys Leu Thr Leu Leu Gly Phe Leu Glu Lys Asn His Ile Pro W0.98/18323 PCT/US97/19575 -184- 55 Gin Lys Leu Tyr Tyr Asn Leu Ser Ser Gin Asp Lys Glu Leu Ser Ala 70 75 Glu Ile Gin Ser Asn Val Thr Tyr Tyr Thr Leu Arg Asp Ala Asn Asn 85 90 Thr Leu Ile Gin Ala Leu Ile Pro Ile Ser Gin Asp Leu Gin Ile His 100 105 110 Ile Tyr Lys Lys Gly Glu Asp Tyr Phe Leu Asp Phe Ile Pro Ile Val 115 120 125 Phe Thr Arg Lys Glu Arg Thr Leu Leu Leu Ser Leu Gin Thr Ser Pro 130 135 140 Tyr Gin Asp Ile Val Lys Ala Thr Asn Asp Pro Leu Leu Ala Asn Gin 145 150 155 160 Leu Met Asn Ala Tyr Lys Lys Ser Val Pro Phe Lys Arg Leu Val Lys 165 170 175 Asn Asp Lys Ile Ala Ile Val Tyr Thr Arg Asp Tyr Arg Val Gly Gin 180 185 190 Ala Phe Gly Gin Pro Thr Ile Lys Met Ala Met Val Ser Ser Arg Leu 195 200 205 His Gin Tyr Tyr Leu Phe Ser His Ser Asn Gly Arg Tyr Tyr Asp Ser 210 215 220 Lys Ala Gin Glu Val Ala Gly Phe Leu Leu Glu Thr Pro Val Lys Tyr 225 230 235 240 Thr Arg Ile Ser Ser Pro Phe Ser Tyr Gly Arg Phe His Pro Val Leu 245 250 255 Lys Val Lys Arg Pro His Tyr Gly Val Asp Tyr Ala Ala Lys His Gly 260 265 270 Ser Leu Ile His Ser Ala Ser Asp Gly Arg Val Gly Phe Ile Gly Val 275 280 285 Lys Ala Gly Tyr Gly Lys Val Val Glu Ile His Leu Asn Glu Leu Arg 290 295 300 Leu Val Tyr Ala His Met Ser Ala Phe Ala Asn Gly Leu Lys Lys Gly 305 310 315 320 Ser Phe Val Lys Lys Gly Gin Ile Ile Gly Arg Val Gly Ser Thr Gly 325 330 335 Leu Ser Thr Gly Pro His Leu His Phe Gly Val Tyr Lys Asn Ser Arg 340 345 350 Pro Ile Asn Pro Leu Gly Tyr Ile Arg Thr Ala Lys Ser Lys Leu His 355 360 365 Gly Lys Gin Arg Glu Val Phe Leu Glu Lys Ala Gin Tyr Ser Lys Gin 370 375 380 Lys Leu Glu Glu Leu Phe Lys Thr His Ser Phe Glu Lys Asn Ser Phe 385 390 395 400 Tyr Leu Leu Glu Gly Phe 405 INFORMATION FOR SEQ ID NO:111: SEQUENCE CHARACTERISTICS: LENGTH: 296 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO-98/18323 WO 9818323PCT/US97/19575 185 (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAI4E/KEY: misc feature LOCATION .296 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:iil: Leu Phe Leu Val Lys Lys Ile Gly Val Vai 1 Phe Gin Asp Gin Asp Ser Asn Lys Gin i4 5 Gly Leu Asn Tyr Giu 225 Asn Lys Ie Phe Leu Giu Tyr Pro Asn Asp Asn Pro 130 Asp Asp Lys Asp Vai 210 Ser Lys Lys Asp Leu 290 Ala Gin Giu Ile Ser Asn Giu 115 Lys Phe Gin Asp Thr 195 Tyr Phe Al a His Leu 275 Giu Cys 20 Giu Val Giu Phe Ser 100 Asp Arg Tyr Trp Gin 180 Lys Thr Leu Leu Sen 260 Asp Cys 5 Ser Asn Phe Giu Asn Giu Asn Lys Pro Leu 165 Asn Thn Thr Leu Asp 245 Thr Phe Leu Gin Asp Ser Arg 70 Pro Lys Al a Thr Leu 150 Ile Asp Gin Asn Giu 230 Thn Asp Lys Lys Giu Gly Giu 55 Asn Giu Asn Asn Lys 135 Lys Giu Lys Ile Asn 215 Lys Met Lys Lys Giu 295 Ser Ser 40 Thn Aia Asn Leu Asn 120 Asn Asn Ile Asp Al a 200 Gly Lys Giu Leu Giu 280 Sen Phe 25 Lys Ile Phe Ser Leu 105 Ser Pro Giy Gin Arg 185 Gin Ser Ser Ile Asp 265 Arg Ile Arg Phe Phe Val1 90 Ser Gin Lys Asp Ser 170 Gin Ile Leu Asp Ser 250 Sen Phe Ile Met Ile Lys Met Gin Pro Ser Tyr Leu Gin Asn Gin Leu Thr 75 Ile Leu Leu Tyr Pro Asn Lys Asn Pro 125 Leu Ile Giu 140 Ile Ile Met 155 Lys Aia Leu Ile Gin Thr Lys Gly Lys 205 Sen Leu Arg 220 Asn Vai Tyr 235 Lys Cys Gin Gin His Lys Lys Ser Asp 285 Leu Lys Val Met Lys Asn Asp 110 Phe Tyr Ser Lys Phe 190 Ile Pro Thr Met Al a 270 Thr Val Lys Asp Val Asp Giu Pro Leu Ser Lys Ang 175 Thr Ser Phe Ile Val 255 Ile Giu Cys Ala Sen Tyr Giu Pro Asn Tyr Gin Giu 160 Phe Phe Ser Tyr Giu 240 Leu Ser Leu INFORMATION FOR SEQ ID NO:ii2: SEQUENCE CHARACTERISTICS: LENGTH: 248 amino acids TYPE: amino acid WO 98/18323 WO 9818323PCT/US97/19575 186- TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .248 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:112:% Vai Ser Tyr Asp Asn Thr Asp Asp Tyr Tyr Phe Pro 1 Ile Leu Tyr Asp 65 Asn Val Giu Giu Phe 145 Phe Val Leu Pro Lys 225 Glu Phe Asn Gly s0 Leu Thr Thr Phe Leu 130 Phe Phe Val Gin Ile 210 Gly Phe Sen Ser Lys Ile Asp Thr Gly 115 Ser Asp Tyr Gly Ile 195 Ala Leu Ser 5 Tyr Asn Al a Arg Tyr Ang Trp Gly Gly Al a 165 Gly Tnp Phe Phe Gly 245 Thr Leu Tyr 55 Lys Pro Phe Gly Leu 135 Leu Thr Glu Ser Gln 215 Pro Arg Met Gly 40 His Thr Leu Arg Gly 120 Lys Thr Thr Arg Pro 200 Trp Asn Phe Sen Gly His Gin Asn Asn 105 Asp Ala Phe Thr Ala 185 Met Gly Met 10 Gly Asn Leu Gly Sen 90 Gly Gly Ala Lys Ala 170 Thr Gly Asp Asn Leu Val1 Gin Gly 75 Thr Ser Ile Lys Thr 155 Asn Trp Pro Gly Asp 235 Pro Arg Lys Tyr Phe Ile Phe Met 140 Pro Phe Arg Leu Asn 220 Tyr Arg Ser Asn Tyr Ile Tyr Thr Thr 125 Arg Thr Lys Ala Val 205 Gly Thr Asn Ser Thr Leu Phe Met Pro 110 Al a Leu Arg Asp Ser 190 Leu Lys Gin Gly Gly Lys Leu Arg Gly Lys Ser Ala Gly Tyr 175 Thr Ile Lys His Val Thr Val Ile Tyr Gly Asp Thr Trp Ser 160 Gly Gly Phe Cys Phe 240 INFORMATION FOR SEQ ID NO:113: SEQUENCE CHARACTERISTICS: LENGTH: 335 amino acids TYPE: amino acid TOPOLOGY: linear f'lYI WO 98/18323 PCT/US97/19575 -187- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...335 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113: Val Gin His Phe Asn Phe Leu Tyr Lys Asp Ser Leu Phe Ser Ile Ala 1 5 10 Leu Phe Thr Phe Ile Ile Ala Leu Val Ile Leu Leu Glu Gin Ala Arg 25 Ala Tyr Phe Thr Arg Lys Arg Asn Lys Lys Phe Leu Gin Lys Phe Ala 40 Gln Asn Gin Asn Ala Tyr Ala Ser Ser Glu Asn Leu Asp Glu Leu Leu 55 Lys His Ala Lys Ile Ser Ser Leu Met Phe Leu Ala Arg Ala Tyr Ser 70 75 Lys Ala Asp Val Glu Met Ser Ile Glu Ile Leu Lys Gly Leu Leu Asn 85 90 Arg Pro Leu Lys Asp Glu Glu Lys Ile Ala Val Leu Asp Leu Leu Ala 100 105 110 Lys Asn Tyr Phe Ser Val Gly Tyr Leu Gin Lys Thr Lys Asp Thr Val 115 120 125 Lys Glu Ile Leu Arg Phe Ser Pro Arg Asn Val Glu Ala Leu Leu Lys 130 135 140 Leu Leu His Ala Tyr Glu Leu Glu Lys Asp Tyr Ser Lys Ala Leu Glu 145 150 155 160 Thr Leu Glu Cys Leu Glu Glu Leu Glu Val Pro Lys Ile Glu Thr Ile 165 170 175 Lys Asn Tyr Leu Tyr Leu Met His Leu Ile Glu Asn Lys Glu Asp Ala 180 185 190 Ala Lys Ile Leu His Val Ser Lys Ala Ser Leu Asp Leu Lys Lys Ile 195 200 205 Ala Leu Asn His Leu Lys Ser His Asp Glu Asn Leu Phe Trp Gin Glu 210 215 220 Ile Asp Thr Thr Glu Arg Leu Glu Asn Val Ile Asp Leu Leu Trp Asp 225 230 235 240 Met Asn Ile Pro Ala Phe Ile Leu Glu Lys His Ala Leu Leu Gin Asp 245 250 255 Ile Ala Arg Ser Gin Gly Leu Leu Leu Asp His Lys Pro Cys Gin Ile 260 265 270 Phe Glu Leu Glu Val Leu Arg Ala Leu Leu His Ser Pro Ile Lys Ala 275 280 285 Ser Leu Thr Phe Glu Tyr Arg Cys Lys His Cys Lys Gin Ile Phe Pro 290 295 300 Phe Glu Ser His Arg Cys Pro Val Cys Tyr Gin Leu Ala Phe Met Asp 305 310 315 320 Met Val Leu Lys Ile Ser Lys Lys Thr His Ala Met Gly Val Asp 325 330 335 WO.98/18323 PCT/US97/19575 188- INFORMATION FOR SEQ ID NO:114: SEQUENCE CHARACTERISTICS: LENGTH: 413 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...413 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114: Met Arg Lys Ile Phe Ser Tyr Ile Ser Lys Val Leu Leu Phe Ile Gly 1 5 10 Val Val Tyr Ala Glu Pro Asp Ser Lys Val Glu Ala Leu Glu Gly Arg 20 25 Lys Gin Glu Ser Ser Leu Asp Lys Lys Ile Arg Gin Glu Leu Lys Ser 40 Lys Glu Leu Lys Asn Lys Glu Leu Lys Asn Lys Asp Leu Lys Asn Lys 55 Glu Glu Lys Lys Glu Thr Lys Ala Lys Arg Lys Pro Arg Ala Glu Val 70 75 His His Gly Asp Ala Lys Asn Pro Thr Pro Lys Ile Thr Pro Pro Lys 90 Ile Lys Gly Ser Ser Lys Gly Val Gin Asn Gin Gly Val Gin Asn Asn 100 105 110 Ala Pro Lys Pro Glu Glu Lys Asp Thr Thr Pro Gin Ala Thr Glu Lys 115 120 125 Asn Lys Glu Thr Ser Pro Ser Ser Gin Phe Asn Ser Ile Phe Gly Asn 130 135 140 Pro Asn Asn Ala Thr Asn Asn Thr Leu Glu Asp Lys Val Val Gly Gly 145 150 155 160 Ile Ser Leu Leu Val Asn Gly Ser Pro Ile Thr Leu Tyr Gin Ile Gin 165 170 175 Glu Glu Gin Glu Lys Ser Lys Val Ser Lys Ala Gin Ala Arg Asp Arg 180 185 190 Leu Ile Ala Glu Arg Ile Lys Asn Gin Glu Ile Glu Arg Leu Lys Ile 195 200 205 His Val Asp Asp Asp Lys Leu Asp Gin Glu Met Ala Met Met Ala Gin 210 215 220 Gin Gin Gly Met Asp Leu Asp His Phe Lys Gin Met Leu Met Ala Glu 225 230 235 240 Gly His Tyr Lys Leu Tyr Arg Asp Gin Leu Lys Glu His Leu Glu Met 245 250 255 Gin Glu Leu Leu Arg Asn Ile Leu Leu Thr Asn Val Asp Thr Ser Ser 260 265 270 I. *1 WO 98/18323 PCTIUS97/19575 189- Glu Ile Asp 305 Ser Ala Asn Gly Lys 385 Lys Thr Pro 290 Leu Lys Gin Gly Lys 370 Leu Leu Met Glu Arg Asn Phe 340 Gly Glu Glu Val Glu Glu Met 310 Lys Ser Gin Ser Ser 390 Ser Tyr Thr 295 Ala Ile His Phe Phe 375 Lys Arg Tyr 280 Val Asp Glu Glu Ile 360 Ser Asp Ile Asn Arg Pro Met Gin 345 Thr Gin Lys Val His Thr Leu 315 Thr Ser Tyr Lys Leu 395 Ile Lys Ser 300 Glu Leu Phe Ile Gin 380 Glu Arg Glu 285 Thr Val Asn Thr Lys 365 Phe Glu Glu Gin Asn Pro Pro Pro 350 Glu Ile His Phe Gin Gly Gin 335 Val Lys Ala Phe Ser Glu Val 320 Ile Met Arg Gin Glu 400 INFORMATION FOR SEQ ID NO:115: Met 1 Leu Gly Asn Asn Thr Gly Gly SEQUENCE CHARACTERISTICS: LENGTH: 186 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...186 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115: Ile Lys Arg Ile Ala Cys Ile Leu Ser Leu Ser 5 10 Ala Gly Glu Val Asn Gly Phe Phe Met Gly Ala 25 Arg Tyr Gly Pro Tyr Asn Ser Asn Tyr Ser Asp 35 40 Asp Leu Tyr Gly Leu Asn Phe Lys Leu Gly Phe 55 Lys Trp Phe Gly Ala Arg Val Tyr Gly Phe Leu 70 75 Ser Gly Thr Glu His Thr Lys Thr Asn Leu Leu 90 Gly Asp Leu Ile Val Asn Leu Ile Pro Leu Asp 100 105 SLeu Ile Gly Gly Val Gin Leu Ala Gly Asn Thr 115 120 Ala Ser Gly Tyr Trp Arg Val Gly Asp Trp Thr Tyr Lys Phe 110 Trp Met 125 Leu Gin His Phe Phe Gly Ala Phe Ala Gin Gly Ala Asn Gly Leu Pro WO 98/18323 PCT/US97/19575 -190- Tyr Asp Val Asn Gin Thr Arg Phe Gin Phe Leu Trp Asn Leu Gly Gly 130 135 140 Arg Met Arg Val Gly Asp Arg Ser Ala Phe Glu Ala Gly Val Lys Phe 145 150 155 160 Pro Met Val Asn Gin Gly Ser Lys Asp Val Gly Leu Ile Arg Tyr Tyr 165 170 175 Ser Trp Tyr Val Asp Tyr Val Phe Thr Phe 180 185 INFORMATION FOR SEQ ID NO:116: SEQUENCE CHARACTERISTICS: LENGTH: 242 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...242 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116: Met Lys Lys Phe Phe Ser Gin Ser Leu Leu Ala Leu Ile Ile Ser Met 1 5 10 Asn Ala Val Ser Gly Met Asp Gly Asn Gly Val Phe Leu Gly Ala Gly 25 Tyr Leu Gin Gly Gin Ala Gin Met His Ala Asp Ile Asn Ser Gin Lys 35 40 Gin Ala Thr Asn Ala Thr Ile Lys Gly Phe Asp Ala Leu Leu Gly Tyr 55 Gin Phe Phe Phe Glu Lys His Phe Gly Leu Arg Leu Tyr Gly Phe Phe 70 75 Asp Tyr Ala His Ala Asn Ser Ile Lys Leu Lys Asn Pro Asn Tyr Asn 90 Ser Glu Ala Ala Gin Val Ala Ser Gin Ile Leu Gly Lys Gin Glu Ile 100 105 110 Asn Arg Leu Thr Asn Ile Ala Asp Pro Arg Thr Phe Glu Pro Asn Met 115 120 125 Leu Thr Tyr Gly Gly Ala Met Asp Val Met Val Asn Val Ile Asn Asn 130 135 140 Gly Ile Met Ser Leu Gly Ala Phe Gly Gly Ile Gin Leu Ala Gly Asn 145 150 155 160 Ser Trp Leu Met Ala Thr Pro Ser Phe Glu Gly Ile Leu Val Glu Gin 165 170 175 Ala Leu Val Ser Lys Lys Ala Thr Ser Phe Gin Phe Leu Phe Asn Val 180 185 190 Gly Ala Arg Leu Arg Ile Leu Lys His Ser Ser Ile Glu Ala Gly Val 195 200 205 WO 98/18323 PCT/US97/19575 -191- Lys Phe Pro Met Leu Lys Lys Asn Pro Tyr Ile Thr Ala Lys Asn Leu 210 215 220 Asp Ile Gly Phe Arg Arg Val Tyr Ser Trp Tyr Val Asn Tyr Val Phe 225 230 235 240 Thr Phe INFORMATION FOR SEQ ID NO:117: SEQUENCE CHARACTERISTICS: LENGTH: 256 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...256 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117: Met Gly Tyr Ala Ser Lys Leu Ala Leu Lys Ile Cys Leu Val Gly Leu 1 5 10 Cys Leu Phe Ser Thr Leu Gly Ala Glu His Leu Glu Gin Lys Gly Asn 25 Tyr Ile Tyr Lys Gly Glu Glu Ala Tyr Asn Asn Lys Glu Tyr Glu Arg 40 Ala Ala Ser Phe Tyr Lys Ser Ala Ile Lys Asn Gly Glu Ser Leu Ala so 55 Tyr Ile Leu Leu Gly Ile Met Tyr Glu Asn Gly Arg Gly Val Pro Lys 70 75 Asp Tyr Lys Lys Ala Val Glu Tyr Phe Gin Lys Ala Val Asp Asn Asp 90 Ile Pro Arg Gly Tyr Asn Asn Leu Gly Val Met Tyr Lys Glu Gly Lys 100 105 110 Gly Val Pro Lys Asp Glu Lys Lys Ala Val Glu Tyr Phe Arg Ile Ala 115 120 125 Thr Glu Lys Gly Tyr Thr Asn Ala Tyr Ile Asn Leu Gly Ile Met Tyr 130 135 140 Met Glu Gly Arg Gly Val Pro Ser Asn Tyr Ala Lys Ala Thr Glu Cys 145 150 155 160 Phe Arg Lys Ala Met His Lys Gly Asn Val Glu Ala Tyr Ile Leu Leu 165 170 175 Gly Asp Ile Tyr Tyr Ser Gly Asn Asp Gin Leu Gly Ile Glu Pro Asp 180 185 190 Lys Asp Lys Ala Val Val Tyr Tyr Lys Met Ala Ala Asp Val Ser Ser 195 200 205 Ser Arg Ala Tyr Glu Gly Leu Ser Glu Ser Tyr Arg Tyr Gly Leu Gly 210 215 220 WO 98/18323 PCT/US97/19575 -192- Val Glu Lys Asp Lys Lys Lys Ala Glu Glu Tyr Met Gin Lys Ala Cys 225 230 235 240 Asp Phe Asp Ile Asp Lys Asn Cys Lys Lys Lys Asn Thr Ser Ser Arg 245 250 255 INFORMATION FOR SEQ ID NO:118: SEQUENCE CHARACTERISTICS: LENGTH: 657 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...657 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118: Met Arg Lys Leu Phe Ile Pro Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 Asn Glu Lys Asn Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr Gly Leu 25 Leu Glu Gly Thr Gin Thr Gin Glu Lys Arg His Thr Thr Thr Lys Asn 40 Thr Tyr Ala Thr Tyr Asn Tyr Leu Pro Thr Asp Thr Ile Leu Lys Arg 55 Ala Ala Asn Leu Phe Thr Asn Ala Glu Ala Ile Ser Lys Leu Lys Phe 65 70 75 Ser Ser Leu Ser Pro Val Arg Val Leu Tyr Met Tyr Asn Gly Gin Leu 90 Thr Ile Glu Asn Phe Leu Pro Tyr Asn Leu Asn Asn Val Lys Leu Ser 100 105 110 Phe Thr Asp Ala Gin Gly Asn Val Ile Asp Leu Gly Val Ile Glu Thr 115 120 125 Ile Pro Lys His Ser Lys Ile Val Leu Pro Gly Glu Ala Phe Asp Ser 130 135 140 Leu Lys Ile Asp Pro Tyr Thr Leu Phe Leu Pro Lys Ile Glu Ala Thr 145 150 155 160 Ser Thr Ser Ile Ser Asp Ala Asn Thr Gin Arg Val Phe Glu Thr Leu 165 170 175 Asn Lys Ile Lys Thr Asn Leu Val Val Asn Tyr Arg Asn Glu Asn Lys 180 185 190 Phe Lys Asp His Glu Asn His Trp Glu Ala Phe Thr Pro Gin Thr Ala 195 200 205 Glu Glu Phe Thr Asn Leu Met Leu Asn Met Ile Ala Val Leu Asp Ser 210 215 220 Gin Ser Trp Gly Asp Ala Ile Leu Asn Ala Pro Phe Glu Phe Thr Asn 225 230 235 240 WO 98/18323 WO 9818323PCTIUS97/19575 193 Ser Thr Lys Ile Pro 305 Ala Ile Lys Thr Ser 385 Gin Al a Gin Ser Ala 465 Val Ile Phe Ala Leu 545 Gly Giy Gly His Ala 625 Asn Phe Pro Asn Gin Val 290 Ser Ser Asn Gly Lys 370 Asp Pro Asp Leu Gin 450 Asn Thr Leu Ile Val 530 Leu Ile Leu Ser Ser 610 Ser Glu Thr Gly Asp 275 Leu Asn Al a Leu Tyr 355 Asp Gly Ala Val Ile 435 Thr Ser Asn Gly Gly 515 Asn Leu Gin Arg Gly 595 Lys Val1 Gly Asp Leu 260 Ile Lys Asn Leu Giu 340 Gly Gly Leu Phe Pro 420 Asn Asn Met His Vai 500 Leu Gin Asp Thr Giy 580 Asn Tyr Val Ala Cys 245 Vai Val Asp Asp Asp 325 Asp His Gin Pro Pro 405 Ala Gin Tyr Leu His 485 Asn Ala Lys Phe Lys 565 Leu Leu Ser Ser Ser 645 Asp Asn Asn Ser Asp 310 Pro Leu Asn Val Tyr 390 Ser Gly Asn Asn Ser 470 Phe Ala Tyr Vai Ile 550 Arg Tyr Asp Val Ser 630 His Asn Ser Lys Gly 295 Gly Lys Arg Gly Glu 375 Asn Asn Phe Ala Leu 455 Thr Ser Lys Tyr Gin 535 Thr Asn Asn -Val Giy 615 Giy Phe Asp Lys Phe 280 Val Lys Lys Thr Asn 360 Lys Val1 Tyr Leu Leu 440 Asn Ile Asn Ile Gly 520 Gin Thr Phe Ser Aia 600 Ile Gly Lys Pro Val 265 Lys Vali His Leu Ile 345 Met Asp Cys Pro Gly 425 Pro Al a Gin Ala Gly 505 Ile Leu Tyr Ser Tyr 585 Thr Ser Asp Val Ser 250 Asp Asn Gly Tyr Phe 330 Leu Thr Ser Ser Asn 410 Val Ile Ser Lys Ser 490 Tyr Ile Ser Ser Ser 570 Tyr Giy Ile Tyr Phe 650 Lys Gin Lys Leu Gly 315 Gly His Tyr Asn Leu 395 Ser Thr Asn Leu Thr 475 Gin Gin Lys Tyr Asn 555 Ser Val Leu Pro Thr 635 Phe Cys Lys Ala Gly 300 Gin Asp Giu Gin Gly 380 Tyr Ile Ala Tyr Asn 460 Phe Ser Asn Tyr Giy 540 Lys Phe Leu Asn Leu 620 Asn Asn Val Tyr Asp 285 Ser Leu Asn Phe Arg 365 Lys Giy Tyr Ala Aia 445 Thr Vai Phe Tyr Asn 525 Gly Asn Gly Asn Tyr 605 Ile Ser Tyr Asn Pro 255 Val Leu 270 Leu Asp Asp Ile Gly Vai Leu Lys 335 Ser His 350 Val Pro Pro Lys Gly Ser His Asn 415 Val Trp, 430 Asn Leu Gin Asp Thr Ser Arg Ser 495 Phe Asn 510 Tyr Ala Gly Ile Ser Pro Ile Phe 575 Lys Val 590 Arg Tyr Gin Arg Phe Vai Gly Trp 655 Giy Asn Val1 Thr Val 320 Thr Thr Val Asp Asn 400 Cys Gin Gly Leu Ser 480 Pro Asp Lys Asp Thr 560 Gly Lys Lys Lys Phe 640 Val WO 98/18323 PCT/US97/19575 194- INFORMATION FOR SEQ ID NO:119: SEQUENCE CHARACTERISTICS: LENGTH: 167 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...167 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119: Met Lys Leu Val Ser Leu Ile Val Ala Leu Val Phe Cys Cys Phe Leu 1 5 10 Gly Ala Val Glu Leu Pro Gly Val Tyr Gin Thr Gin Glu Phe Leu Tyr 25 Met Lys Ser Ser Phe Val Glu Phe Phe Glu His Asn Gly Lys Phe Tyr 40 Ala Tyr Gly Ile Ser Asp Val Asp Gly Ser Lys Ala Lys Lys Asp Lys 55 Leu Asn Pro Asn Pro Lys Leu Arg Asn Arg Ser Asp Lys Gly Val Val 65 70 75 Phe Leu Ser Asp Leu Ile Lys Val Gly Glu Gin Ser Tyr Lys Gly Gly 90 Lys Ala Tyr Asn Phe Tyr Asp Gly Lys Thr Tyr His Val Arg Val Thr 100 105 110 Gin Asn Ser Asn Gly Asp Leu Glu Phe Thr Ser Ser Tyr Asp Lys Trp 115 120 125 Gly Tyr Val Gly Lys Thr Phe Thr Trp Lys Arg Leu Ser Asp Glu Glu 130 135 140 Ile Lys Asn Leu Lys Leu Lys Arg Phe Asn Leu Asp Glu Val Leu Lys 145 150 155 160 Thr Leu Lys Asp Ser Pro Ile 165 INFORMATION FOR SEQ ID NO:120: SEQUENCE CHARACTERISTICS: LENGTH: 294 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: WO 98/18323 WO 9818323PCTIUS97/19575 195 ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .294 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120: Met Ser Asn Gin Ala Ser His Leu Asp Asn Phe Met 1 Pro Thr Ala Asp Lys Ile Giu Val Thr 145 Asp Ala Leu Giu His 225 Arg Gin Gly Leu Lys Ser Tyr Ile Asn Cys Giu Asp 130 Gly Cys Tyr Ile Arg 210 Tyr Glu Ser Thr Leu 290 Ser Gly Ser Gly Ile Giu Ile 115 Glu Ala Val Ala Ala 195 Leu Leu Arg Ile Leu 275 Lys Phe Lys Leu Leu Leu Ile 100 Leu Giu Gly Val Cys 180 Asn Phe Giy Lys Asp 260 Giu Tyr 5 Phe Gly Tyr Ala His 85 Glu Lys Gly Ile Ile 165 Ile Met Lys Ala Ile 245 Gin Ile Leu Asp Gly Lys Asn 70 Al a Pro Tyr Val1 Gly 150 Val Lys Val Val Ile 230 Leu Ile Pro Giy Asn Vai Lys Leu Leu Gly Ile Leu 135 Al a Thr Ile Al a Al a 215 Glu Arg Ala Lys Lys Gly 40 Gly Asp Lys Leu Ser 120 Ser Thr Thr Asn Gin 200 Lys Asn Lys Ser Giu 280 Gly 25 Lys Tyr Val Gly Cys 105 Gly Sen Thr Pro Ser 185 Pro Asn Sen Ile Leu 265 Gly 10 Asn Sen Lys Ile Glu 90 Leu Al a Leu Gin Asp 170 Lys Lys Asn Sen Ala 250 Leu Leu Thr Asn Val Phe 75 Al a Ile Glu Asp Al a 155 Pro Asn Giu Ile Leu 235 Pro Val1 Lys Asn Phe Ser Val Val1 Leu Gly Leu 125 Ile Leu Al a Asp Arg 205 Ser Lys Asp Lys Phe 285 Al a Ile Ala Phe Lys Gln Asp 110 Asp Val Asn Ile Glu 190 Al a Leu Ang Leu Leu 270 Phe Lys Ala Asn Asp Thr Glu Ser Arg Ile Al a Thr 175 Leu Thr Giu Tyr Phe 255 Giu Lys Asn Ile Leu Ala His Ile Gly Phe Asp Ser 160 Asp Phe Tyr Leu Val 240 Ser Thr Arg INFORMATION FOR SEQ ID NO:12i: SEQUENCE CHARACTERISTICS: LENGTH: 372 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/18323 PCT/US97/19575 -196- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...372 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121: Leu Glu Pro Ser Arg Asn Arg Leu Lys His Ala Ala Phe Phe Val Gly 1 5 10 Leu Phe Ile Val Leu Phe Leu Ile Ile Met Lys His Gin Thr Ser Pro 25 Tyr Ala Phe Thr His Asn Gin Ala Leu Val Thr Gin Thr Pro Pro Tyr 40 Phe Thr Gin Leu Thr Ile Pro Lys Pro Asn Asp Ala Leu Ser Ala His 50 55 Ala Ser Ser Leu Ile Ser Leu Pro Asn Asp Asn Leu Leu Ser Ala Tyr 70 75 Phe Ser Gly Thr Lys Glu Gly Ala Arg Asp Val Lys Ile Ser Ala Asn 90 Leu Phe Asp Ser Lys Thr Asn Arg Trp Ser Glu Ala Phe Ile Leu Leu 100 105 110 Thr Lys Glu Glu Leu Ser His His Ser His Glu Tyr Ile Lys Lys Leu 115 120 125 Gly Asn Pro Leu Leu Phe Leu His Asp Asn Lys Ile Leu Leu Phe Val 130 135 140 Val Gly Val Ser Met Gly Gly Trp Ala Thr Ser Lys Ile Tyr Gin Phe 145 150 155 160 Glu Ser Ala Leu Glu Pro Ile His Phe Lys Phe Ala Arg Lys Leu Ser 165 170 175 Leu Ser Pro Phe Leu Asn Leu Ser His Leu Val Arg Asn Lys Pro Leu 180 185 190 Asn Thr Thr Asp Gly Gly Phe Met Leu Pro Leu Tyr His Glu Leu Ala 195 200 205 Thr Gin Tyr Pro Leu Leu Leu Lys Phe Asp Gin Gin Asn Asn Pro Arg 210 215 220 Glu Leu Leu Arg Pro Asn Thr Leu Asn His Gin Leu Gin Pro Ser Leu 225 230 235 240 Thr Pro Phe Lys Asp Cys Ala Val Met Ala Phe Arg Asn His Ser Phe 245 250 255 Lys Asp Ser Leu Met Leu Glu Thr Cys Lys Thr Pro Thr Asp Trp Gin 260 265 270 Lys Pro Ile Ser Thr Asn Leu Lys Asn Leu Asp Asp Ser Leu Asn Leu 275 280 285 Leu Asn Leu Asn Gly Ile Leu Tyr Leu Ile His Asn Pro Ser Asp Leu 290 295 300 Ser Leu Arg Arg Lys Glu Leu Trp Leu Ser Lys Leu Glu Asn Ser Asn 305 310 315 320 Ser Phe Lys Thr Leu Lys Val Leu Asp Lys Ala Asn Glu Val Ser Tyr 325 330 335 Pro Ser Tyr Ser Leu Asn Pro His Phe Ile Asp Ile Val Tyr Thr Tyr WO 98/18323 PCT/US97/19575 -197- 340 345 350 Asn Arg Ser His Ile Lys His Ile Arg Phe Asn Met Ala Tyr Leu Asn 355 360 365 Ser Leu Leu Lys 370 INFORMATION FOR SEQ ID NO:122: SEQUENCE CHARACTERISTICS: LENGTH: 978 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...978 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122: Met Lys Lys Arg Lys His Val Ser Lys Lys Val Phe Asn Val Ile Ile 1 5 10 Leu Phe Val Ala Val Phe Thr Leu Leu Val Val Ile His Lys Thr Leu 20 25 Ser Asn Gly Ile His Ile Gin Asn Leu Lys Ile Gly Lys Leu Gly Ile 40 Ser Glu Leu Tyr Leu Lys Leu Asn Asn Lys Leu Ser Leu Glu Val Glu 55 Arg Val Asp Leu Ser Ser Phe Phe His Gin Lys Pro Thr Lys Lys Arg 70 75 Leu Glu Val Ser Asp Leu Ile Lys Asn Ile Arg Tyr Gly Ile Trp Ala 90 Val Ser Tyr Phe Glu Lys Leu Lys Val Lys Glu Ile Ile Leu Asp Asp 100oo 105 110 Lys Asn Lys Ala Asn Ile Phe Phe Asp Gly Asn Lys Tyr Glu Leu Glu 115 120 125 Phe Pro Gly Ile Lys Gly Glu Phe Ser Leu Glu Asp Asp Lys Asn Ile 130 135 140 Lys Leu Lys Ile Ile Asn Leu Leu Phe Lys Asp Val Lys Val Gin Val 145 150 155 160 Asp Gly Asn Ala His Tyr Ser Pro Lys Ala Arg Lys Met Ala Phe Asn 165 170 175 Leu Ile Val Lys Pro Leu Val Glu Pro Ser Ala Ala Ile Tyr Leu Gin 180 185 190 Gly Leu Thr Asp Leu Lys Thr Ile Glu Leu Lys Ile Asn Thr Ser Pro 195 200 205 Met Lys Ser Leu Ala Phe Leu Lys Pro Leu Phe Gin Arg Gin Ser Gin 210 215 220 Lys Asn Leu Lys Thr Trp Ile Phe Asp Lys Ile Gin Phe Ala Ser Phe WO 98/18323 PCT/US97/19575 -198- 225 230 235 240 Lys Ile Asp Asn Ala Leu Ile Lys Ala Asn Phe Thr Pro Ser Glu Phe 245 250 255 Ile Pro Ser Leu Leu Glu Asn Ser Val Val Lys Ala Thr Leu Ile Lys 260 265 270 Pro Ser Val Val Phe Asn Asp Gly Leu Ser Pro Ile Lys Met Asp Lys 275 280 285 Thr Glu Leu Ile Phe Lys Asn Lys Gin Leu Leu Ile Gin Pro Gin Lys 290 295 300 Ile Thr Tyr Glu Thr Met Glu Leu Thr Gly Ser Tyr Ala Thr Phe Ser 305 310 315 320 Asn Leu Leu Glu Ala Pro Lys Leu Glu Val Phe Leu Lys Thr Thr Pro 325 330 335 Asn Tyr Tyr Gly Asp Ser Ile Lys Asp Leu Leu Ser Ala Tyr Lys Val 340 345 350 Val Leu Pro Leu Asp Lys Ile Ser Met Pro Ser Ser Ala Asp Leu Lys 355 360 365 Leu Thr Leu Gin Phe Leu Lys Asn Thr Ala Pro Leu Phe Ser Val Gin 370 375 380 Gly Ser Val Asn Leu Gin Glu Gly Thr Phe Ser Leu Tyr Asn Ile Pro 385 390 395 400 Leu Tyr Thr Gin Ser Ala Gin Ile Asn Leu Asp Ile Ala Gin Glu Tyr 405 410 415 Gin Tyr Ile Tyr Ile Asp Thr Ile His Thr Arg Tyr Ala Asn Met Leu 420 425 430 Asp Leu Asp Ala Lys Ile Ala Leu Asp Leu Gly Gin Lys Asn Leu Ser 435 440 445 Leu Asp Ser Leu Val His Lys Ile Gin Val Asn Thr Asn Asn Asn Ile 450 455 460 Asn Met Arg Ser Tyr Asp Pro Asn Asn Thr Gin Glu Asp Pro Gin Thr 465 470 475 480 Asn Phe Thr Leu Asp Leu Lys Ser Leu His Ser Ile Ile Gin Glu Gly 485 490 495 Glu Asn Ser Glu Val Phe Arg Arg Lys Ile Ile Asp Thr Ile Lys Ala 500 505 510 Gin Ser Glu Asp Lys Phe Thr Lys Asp Val Phe Tyr Ala Thr Gly Asp 515 520 525 Thr Leu Lys Ser Leu Ser Leu Ser Phe Asp Phe Ser Asn Pro Asp His 530 535 540 Ile Gin Trp Ser Val Pro Gin Leu Leu Leu Glu Gly Glu Phe Lys Asp 545 550 555 560 Asn Ala Tyr Thr Phe Lys Ile Lys Asp Leu Lys Lys Ile Lys Pro Tyr 565 570 575 Ser Pro Ile Met Asp Tyr Ile Ala Leu Lys Asp Gly Ser Leu Glu Val 580 585 590 Ser Thr Ser Asp Phe Val Asn Ile Asp Phe Phe Ala Lys Asp Leu Lys 595 600 605 Ile Asn Leu Pro Ile Tyr Arg Ser Asp Gly Ser His Phe Asp Ser Phe 610 615 620 Ser Leu Phe Gly Ser Ile Asn Lys Asp Glu Ile Ser Val Tyr Thr Pro 625 630 635 640 Ser Lys Ser Ile Ser Ile Lys Val Lys Gly Asp Gin Lys Asp Ile Thr 645 650 655 Leu Asn Asn Ile Asp Leu Ser Ile Asp Asp Phe Leu Asp Ser Lys Met 660 665 670 WO 98/18323 WO 9818323PCTIUS97/19575 -199 Pro Ser Tyr 705 Lys Leu Lys Lys Asp 785 Gin Phe Leu Lys Giu 865 Ile Thr Tyr Lys Ile 945 Asp Leu Al a Lys 690 Giu Asp Asp Asn Ala 770 Phe Val Ala Ile Thr 850 Lys Ile Ile Leu Giy 930 Ile Ile Lys Ile 675 Giu Lys Vai Ile Al a 755 His Vai Phe Leu Val 835 Gly Ile Giu Lys Val 915 Thr Gin Ile Aia Ile Al a Val Val1 740 Met Asn Giu Asn Met 820 Phe Ser Asp Leu Aia 900 Leu Leu Aia Val Gly Gin His Leu 725 Ala Ile Phe Gly Gly 805 Gin Arg Val Leu Asp 885 Leu Gly Asp Pro Asp 965 Leu Asp Lys 710 Ile Gin Met Ser Giy 790 Glu Asn Asn Val Val 870 Lys Ser Lys Lys Phe 950 Giu Phe Giu 695 Ile Tyr Asp Ala Gly 775 Leu Leu Met Pro Phe 855 Gly Asn Asn Gly Pro 935 Lys Val Lys Val Pro Lys Arg 745 Leu Tyr Thr Phe Asn 825 Leu Ile Thr Leu Leu 905 Lys Thr Leu Lys Giu Phe Ile Met 730 Val Val Ile Leu Gin 810 Leu Gly Thr Leu Asp 890 Asn Ile Gin Arg Asn 970 Arg Ile Ser 715 Pro Lys His Asn Ile 795 Asn Ile Ala Lys Asp 875 Leu Lys Thr Val Arg 955 Ile Lys Ser 700 Thr Phie Ile Gly Thr 780 Gly Thr Asn Asn Giu 860 Ile Asn Ile Thr Thr 940 Ile Asp Lys Lys Ile Leu Gly 750 Leu Leu Leu Leu Ile 830 Tyr Leu Giy Giu Ile 910 Val Aia Thr Lys Pro Gin His Giu 735 Asn Tyr Gin Glu Lys- 815 Pro Gin Gly Asn Val 895 Val Asn Ser Pro Arg 975 Ser Arg Ala 720 Asn Tyr Leu Lys Asp 800 Asn Ser Ile Leu Gly 880 Ser Gly Val Asp Ile 960 Lys INFORMATION FOR SEQ ID NO:123: SEQUENCE CHARACTERISTICS: LENGTH: 477 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/18323 PCT/US97/19575 -200- (ix) FEATURE: NAME/KEY: misc-feature LOCATION .477 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123: Met Asn Thr Ile Ile Arg Tyr Ala Ser Leu Trp Gly 1 Leu Ile Thr Thr Asp Asn Asn Tyr Asn 145 Phe Thr Val Leu Lys 225 Lys Ala Val Arg Arg 305 Asp Phe Thr Ile Leu Thr Leu Ser Al a Lys Leu His Asn 130 Thr Ser Val Gin Gin 210 Leu Al a Leu Lys Giu 290 Tyr Ser Gly Leu Met 370 Glu Leu Asn Ser Thr Al a Ser Thr 115 Phe Gin Asn Ala Gin 195 Lys Tyr Gin Giu Asn 275 Arg Gin Trp Asn Asn 355 Leu Gin Al a 20 Asn Leu Thr Ala Leu 100 Ile Lys Gin Val Asn 180 Tyr Lys Asp Gly Gin 260 Leu Gin Asn Leu Phe 340 Ile Gly Giu 5 Gin Tyr Giu Ile Leu Gin Al a Asn Leu Asn 165 Leu Tyr Leu Lys Asn 245 Asn Lys Asp Lys Phe 325 Tyr Phe Gin Lys Thr Ser Ala Asn 70 Gly Ala Lys Giu Gin 150 Asn Giu Giu Giu Gly 230 Leu Arg Lys Leu Gin 310 Trp Pro Asp Leu Asp Pro His Thr 55 Gin Leu Gin Ala Ala 135 Ala Val1 Tyr Tyr Gin 215 Leu Ser Leu Thr Val 295 Leu Ile Gly Asp Ala 375 Glu Ser Lys 40 Pro Glu Tyr Glu Met 120 Arg Gin Lys Ser Phe 200 Ile Thr Giu Thr Thr 280 Ser Asn Gin Gin Ile 360 Asn Gin Lys 25 Asn Gly Ile Glu Leu 105 Phe Asp Val Giu Arg 185 Asn Gin Thr Tyr Leu 265 Ile Leu Tyr Lys Gin 345 Gly Glu Leu Pro Lys Leu Lys 75 Leu Val Pro Pro Leu 155 Ser Ser Leu Asp Asp 235 Ile Tyr Ala Giu Pro 315 Al a Thr Ser Asn Arg Asp Leu Pro Tyr Lys Lys Thr Glu 140 Asn Ala Val Ala Ile 220 Asp Leu Leu Pro Gin 300 Lys Tyr Ala Leu Leu 380 Lys Leu Giu Ile Ser His Gly Gin Leu 125 Tyr Val Thr Tyr Arg 205 Lys Leu Asp Thr Asn 285 Ile Ile Al a Gly Gin 365 Al a Ser Cys Ile Asp Pro Glu Ala Ala 110 Asn Lys Phe Tyr Leu 190 Met Arg Gin Met Asn 270 Leu Ser Asp Thr Val1 350 Lys Tyr Leu Ile Lys Pro Lys Lys Thr Met Ala His Asn Arg 175 Gin Ile Val Ser Gin 255 Leu Gin Ala Val Gly 335 Thr Gin Lys Asp Thr Gin Pro Giu Ser Thr Lys Ser Tyr Gly 160 Ser Val Ala Thr Leu 240 Phe Ser Leu Leu Phe 320 Arg Al a Ser Lys Ile WO 98/18323 PCT/US97/19575 -201- 385 390 395 Ala Arg Ala Lys Ile Glu Ser Ser Lys Ala Ser Leu 405 410 Leu Ser Phe Ala Asn Ile Lys Arg Lys Tyr Asp Ala 420 425 Phe Thr Thr Tyr Leu Arg Gly Leu Thr Thr Arg Phe 435 440 Ala Tyr Asn Leu Ala Leu Asn Asn Tyr Glu Val Gin 450 455 460 Ile Phe Asn Ser Gly His Lys Ile Asp Asp Tyr Val 465 470 475 INFORMATION FOR SEQ ID NO:124: SEQUENCE CHARACTERISTICS: LENGTH: 412 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...412 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124: Met Leu Ser Phe Ile Ser Ala Phe Asp Lys Arg Gly Asp Ala Ala 415 Asn Leu Val 430 Asp Ala Glu 445 Lys Ala Asn His 400 Asn Asp Val Tyr Arg Asp Lys Lys Asn Asn Leu Glu Gly Ala 160 Ser Leu 1 Leu Leu Ile Val Ala Met Thr Leu Ile 145 Ile Pro Leu Glu Gin 50 Val Asn Ser Gin Lys 130 Glu Lys Asp Thr Ile Ala Ser Val Leu Ser 115 Lys Asn Asn Leu Ala Gin Leu Lys Ser Gly 100 Lys Thr Tyr Leu Ile 5 Leu Thr Gin Trp Asp Leu Met Lys Lys Glu 165 Ala Leu Phe Glu Asp 70 Phe Ser Ile Gin Asn 150 Asn Ile Leu Val Gin Asn Phe Gin Asn Gin 135 Gin Thr Ala Leu Ala 40 Ile Pro Arg Lys Leu 120 Leu Gin Leu Lys Phe 25 Lys Asp Ile Leu Val 105 Glu Val Glu Tyr Leu Leu Leu Leu Tyr 75 Ser Leu Gin Asn Glu 155 Ala Ile Val Leu Lys Ser Gly Leu Gly Lys 125 Met Leu His Lys Ser Ala Asn Gin Tyr Met Lys 110 Ile Ile Asn Ser Ser Ile Lys Gin Glu Asn Gin Lys Leu Asn Thr Ser 175 Leu WO 98/18323 PCT/US97/19575 -202 180 185 190 Glu Ile Gin Lys Asn Asp Leu Glu Val Ala Leu Ser Ser Ser His Tyr 195 200 205 Ser Met Gly Glu Leu Thr Phe Lys Glu Asn Glu Ile Leu Ser Ile Ala 210 215 220 Pro Lys Asn Phe Glu Phe Asn Asn Glu Gin Glu Leu His Asn Ile Ser 225 230 235 240 Ala Thr Asn Tyr Asp Ile Ala Ile Ala Arg Leu Asp Glu Glu Lys Ala 245 250 255 Gin Lys Asp Ile Thr Leu Ala Lys Lys Ser Phe Leu Glu Asp Ile Asn 260 265 270 Val Thr Gly Val Tyr Tyr Phe Arg Ser Lys Gin Tyr Tyr Asn Tyr Asp 275 280 285 Met Phe Ser Val Ala Leu Ser Ile Pro Leu Pro Leu Tyr Gly Lys Gin 290 295 300 Ala Lys Leu Val Glu Gln Lys Lys Lys Glu Ser Leu Ala Phe Lys Ser 305 310 315 320 Glu Val Glu Asn Ala Lys Asn Lys Thr Arg His Leu Ala Leu Lys Leu 325 330 335 Leu Lys Lys Leu Glu Thr Leu Gin Lys Asn Leu Glu Ser Ile Asn Lys 340 345 350 Ile Ile Lys Gin Asn Glu Lys Ile Ala Gin Ile Tyr Ala Leu Asp Leu 355 360 365 Lys Thr Asn Gly Asp Tyr Asn Ala Tyr Tyr Asn Ala Leu Asn Asp Lys 370 375 380 Ile Thr Ile Gin Ile Thr Gin Leu Glu Thr Leu Ser Ala Leu Asn Ser 385 390 395 400 Ala Tyr Leu Ser Leu Gin Asn Leu Lys Gly Leu Glu 405 410 INFORMATION FOR SEQ ID NO:125: SEQUENCE CHARACTERISTICS: LENGTH: 137 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...137 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125: Met Arg Ile Val Arg Asn Leu Phe Leu Val Ser Phe Val Ala Tyr Ser 1 5 10 Ser Ala Phe Ala Ala Asp Leu Glu Thr Gly Thr Lys Asn Asp Lys Lys 25 Ser Gly Lys Lys Phe Tyr Lys Leu His Lys Asn His Gly Ser Glu Thr WO 98/18323 WO 9818323PCT/US97/19575 203 40 Glu Thr Lys Asn Asp Lys Lys Leu Tyr Asp Phe Thr 55 Leu Giu Gly Val Asp Leu Glu Lys Ser Pro Asn Leu 65 70 75 Lys Ser Asp Lys Lys Phe Tyr Lys Gin Leu Ala Lys 90 Giu Gly Val Ser Met Pro Ile Val Asn Phe Asn Lys 100 105 Gly Pro Tyr Phe Glu Arg Thr Lys Ser Lys Lys Thr 115 120 Gly Gly Leu Met Met His Ile Arg Phe 130 135 INFORMATION FOR SEQ ID NO:126: SEQUENCE CHARACTERISTICS: LENGTH: 309 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .309 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126: Lys Asn Sen Gly Lys Ser His Lys Asn Asn Ile Ala Ala Leu Ser Phe 110 Gin Tyr Met Asp 125 Leu met Pro Gin Asn Gin Leu Val Ile Thr Ile Ile 1 Ser Ser Lys Val Lys Ile Giy Gin Thr 145 Lys Lys Val1 Phe Leu Glu Arg Gly Lys 130 Tyr Ile Gin Val 35 Leu Arg Ile Gly His 115 His Sen Lys Leu Ile Ile Asp Lys Leu 100 Leu Leu Ala Giy 5 Lys Leu Ala Phe Asn Giu Tyr Ala Ile Val Phe Leu Lys Arg 70 Lys Ser Asp Leu Lys 150 Glu Sen Leu Met 55 Gly Arg Leu Giu Met 135 Pro Ser Lys Asn 25 Ile Val 40 Asp Thr Leu Tyr Giu Giu Ile Glu 105 Val.Asp 120 Leu Ile Thr Lys Gly Ile 10 Leu Lys Giy Leu Met Thr Gin Lys 75 Leu Phe 90 Ile Lys Leu Giu Pro Asn Giu Arg 155 Asp Phe Arg Giy Ser Asn Ile Lys Asn Gly 140 Asn Ile Asp Asn Val Giu Tyr Val1 Gly Leu 125 Met His Al a Glu Leu Gly Arg Ala Gly Ala 110 Ser Pro Pro Pro Ser Ile Phe Asn Leu Gin Asn Leu Leu Ile Leu Giy Ile Leu Aia Ala Lys Gly Asn Lys Lys 160 Asn WO 98/18323 PCT/US97/19575 -204- 165 170 175 Thr Pro Val Tyr Ala Ser Ala Asp Gly Ile Val Asp Phe Val Lys Thr 180 185 190 Arg Ser Asn Ala Gly Tyr Gly Asn Leu Val Arg Ile Glu His Ala Phe 195 200 205 Gly Phe Ser Ser Ile Tyr Thr His Leu Asp His Val Asn Val Gin Pro 210 215 220 Lys Ser Phe Ile Gin Lys Gly Gin Leu Ile Gly Tyr Ser Gly Lys Ser 225 230 235 240 Gly Asn Ser Gly Gly Glu Lys Leu His Tyr Glu Val Arg Phe Leu Gly 245 250 255 Lys Ile Leu Asp Ala Glu Lys Phe Leu Ala Trp Asp Leu Asp His Phe 260 265 270 Gin Ser Ala Leu Glu Glu Asn Lys Phe Ile Glu Trp Lys Asn Leu Phe 275 280 285 Trp Val Leu Glu Asp Ile Val Gin Leu Gln Glu His Val Asp Lys Asp 290 295 300 Thr Leu Lys Gly Gin 305 INFORMATION FOR SEQ ID NO:127: SEQUENCE CHARACTERISTICS: LENGTH: 332 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...332 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127: Val Leu Tyr Phe Leu Thr Ser Leu Phe Ile Cys Ser Leu Ile Val Leu 1 5 10 Trp Ser Lys Lys Ser Met Leu Phe Val Asp Asn Ala Asn Lys Ile Gin 25 Gly Phe His His Ala Arg Thr Pro Arg Ala Gly Gly Leu Gly Ile Phe 40 Leu Ser Phe Ala Leu Ala Cys Tyr Leu Glu Pro Phe Glu Met Pro Phe 55 Lys Gly Pro Phe Val Phe Leu Gly Leu Ser Leu Val Phe Leu Ser Gly 65 70 75 Phe Leu Glu Asp Ile Asn Leu Ser Leu Ser Pro Lys Ile Arg Leu Ile 90 Leu Gin Ala Val Gly Val Val Cys Ile Ile Ser Ser Thr Pro Leu Val 100 105 110 Val Ser Asp Phe Ser Pro Leu Phe Ser Leu Pro Tyr Phe Ile Ala Phe WO 98/18323 PCT/US97/19575 -205- Leu Ile 145 Leu Tyr Phe Ser Leu 225 Arg Leu Pro Ile Ile 305 Asn Phe 130 Asp Val Met Leu Leu 210 Asn Arg His Asn Leu 290 Ser Arg 115 Ala Gly Ile Val Gly 195 Leu Leu Lys Thr Pro 275 Ile Leu Gin Ile Phe His Leu 180 Asp His Met Ile Leu 260 Leu Ser Val Val Phe Asn Tyr 165 Gly Gly Leu Leu Lys 245 Leu Cys Val Phe Cys 325 Met Gly 150 Ile Phe Gly Ser Tyr 230 Arg Phe Ala Leu Ile 310 Ala Leu 135 Leu Asp Met Ala Leu 215 Pro Gin Lys Phe Phe 295 Ala Leu 120 Val Ala Pro Val Tyr 200 Glu Val Lys Phe Ile 280 Arg Cys Glu Gly Ser Ser Leu 185 Phe Gin Ile Ala Leu 265 Leu Leu Tyr Lys Ile Gly Ser 170 Asn Leu Lys Glu Thr 250 Gin Ile Asp Leu Arg 330 Ser Ile 155 Leu Phe Gly Ile Val 235 Met Gin Leu Ala Ile 315 Ala Asn 140 Cys Ser Pro Leu Ser 220 Leu Pro Arg Cys Tyr 300 Gly Phe 125 Ala Ala Cys Ser Val 205 Val Phe Asp Ser Asn 285 Ala Tyr Ile Ile Leu Gly 190 Cys Phe Ser Asn Phe 270 Leu Leu Ala Asn Ala Leu 175 Lys Gly Phe Ile Leu 255 Asn Pro Ile Tyr Ile Leu 160 Ala Ile Ile Gly Leu 240 His Tyr Phe Val Leu 320 INFORMATION FOR SEQ ID NO:128: SEQUENCE CHARACTERISTICS: LENGTH: 271 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1-...271 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128: Met Asn Ile Phe Lys Arg Ile Ile Cys Val Thr Ala Ile Val Leu Gly 1 5 10 Phe Phe Asn Leu Leu Asp Ala Lys His His Lys Glu Lys Lys Glu Asp 25 His Lys Ile Thr Arg Glu Leu Lys Val Gly Ala Asn Pro Val Pro His 40 Ala Gin Ile Leu Gln Ser Val Val Asp Asp Leu Lys Glu Lys Gly Ile W0O98/18323 PCTIU~S97/19575 -206- 55 Lys Leu Val Ile Val Ser Phe Thr Asp Tyr Val Leu Pro Asn Leu Ala 70 75 Leu Asn Asp Gly Ser Leu Asp Ala Asn Tyr Phe Gin His Arg Pro Tyr 85 90 Leu Asp Arg Phe Asn Leu Asp Arg Lys Met His Leu Val Gly Leu Ala 100 105 110 Asn Ile His Val Glu Pro Leu Arg Phe Tyr Ser Gin Lys Ile Thr Asp 115 120 125 Ile Lys Asn Leu Lys Lys Gly Ser Val Ile Ala Val Pro Asn Asp Pro 130 135 140 Ala Asn Gin Gly Arg Ala Leu Ile Leu Leu His Lys Gin Gly Leu Ile 145 150 155 160 Ala Leu Lys Asp Pro Ser Asn Leu Tyr Ala Thr Glu Phe Asp Ile Val 165 170 175 Lys Asn Pro Tyr Asn Ile Lys Ile Lys Pro Leu Glu Ala Ala Leu Leu 180 185 190 Pro Lys Val Leu Gly Asp Val Asp Gly Ala Ile Ile Thr Gly Asn Tyr 195 200 205 Ala Leu Gin Ala Lys Leu Thr Gly Ala Leu Phe Ser Glu Asp Lys Asp 210 215 220 Ser Pro Tyr Ala Asn Leu Val Ala Ser Arg Glu Asp Asn Ala Gin Asp 225 230 235 240 Glu Ala Ile Lys Ala Leu Ile Glu Ala Leu Gin Ser Glu Lys Thr Arg 245 250 255 Lys Phe Ile Leu Asp Thr Tyr Lys Gly Ala Ile Ile Pro Ala Phe 260 265 270 INFORMATION FOR SEQ ID NO:129: SEQUENCE CHARACTERISTICS: LENGTH: 316 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...316 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129: Met Gin Glu Phe Ser Leu Trp Cys Asp Phe Ile Glu Arg Asp Phe Leu 1 s 10 is Glu Asn Asp Phe Leu Lys Leu Ile Asn Lys Gly Ala Ile Cys Gly Ala 25 Thr Ser Asn Pro Ser Leu Phe Cys Glu Ala Ile Thr Lys Ser Ala Phe 40 Tyr Gin Asp Glu Ile Ala Lys Leu Lys Gly Lys Lys Ala Lys Glu Ile WO 98/18323 PCT/US97/19575 -207- 55 Tyr Glu Thr Leu Ala Leu Lys Asp Ile Leu Gin Ala Ser Ser Ala Leu 70 75 Met Pro Leu Tyr Glu Lys Asp Pro Asn Asn Gly Tyr Ile Ser Leu Glu 85 90 Ile Asp Pro Phe Leu Glu Asp Asp Ala Ile Lys Ser Ile Asp Glu Ala 100 105 110 Lys Arg Leu Phe Lys Thr Leu Asn Arg Pro Asn Val Met Ile Lys Val 115 120 125 Pro Ala Ser Glu Ser Ala Phe Glu Val Ile Ser Ala Leu Ala Gin Ala 130 135 140 Ser Ile Pro Ile Asn Val Thr Leu Val Phe Ser Pro Lys Ile Ala Gly 145 150 155 160 Glu Ile Ala Gin Ile Leu Ala Lys Glu Ala Arg Lys Arg Ala Val Ile 165 170 175 Ser Val Phe Val Ser Arg Phe Asp Lys Glu Ile Asp Pro Leu Val Pro 180 185 190 Gin Asn Leu Gin Ala Gin Ser Gly Ile Met Asn Ala Thr Glu Cys Tyr 195 200 205 Tyr Gin Ile Asn Gin His Ala Asn Lys Leu Ile Ser Thr Leu Phe Ala 210 215 220 Ser Thr Gly Val Lys Ser Asn Ser Leu Ala Lys Asp Tyr Tyr Ile Lys 225 230 235 240 Ala Leu Cys Phe Lys Asn Ser Ile Asn Thr Ala Pro Leu Asp Ala Leu 245 250 255 Asn Ala Tyr Leu Leu Asp Pro Asn Thr Glu Cys Gin Thr Pro Leu Lys 260 265 270 Ile Thr Glu Ile Glu Ala Phe Lys Lys Glu Leu Lys Thr His Asn Ile 275 280 285 Asp Leu Glu Asn Thr Ala Gin Lys Leu Leu Lys Glu Gly Leu Ile Ala 290 295 300 Phe Lys Gin Ser Phe Glu Lys Leu Leu Ser Ser Phe 305 310 315 INFORMATION FOR SEQ ID NO:130: SEQUENCE CHARACTERISTICS: LENGTH: 260 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...260 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130: Met Lys Thr Asn Gly His Phe Lys Asp Phe Ala Trp Lys Lys Cys Phe WO 98/18323 PCT/US97/19575 -208- 1 5 10 Leu Gly Ala Ser Val Val Ala Leu Leu Val Gly Cys Ser Pro His Ile 25 Ile Glu Thr Asn Glu Val Ala Leu Lys Leu Asn Tyr His Pro Ala Ser 35 40 Glu Lys Val Gin Ala Leu Asp Glu Lys Ile Leu Leu Leu Arg Pro Ala 55 Phe Gin Tyr Ser Asp Asn Ile Ala Lys Glu Tyr Glu Asn Lys Phe Lys 70 75 Asn Gin Thr Thr Leu Lys Val Glu Glu Ile Leu Gin Asn Gin Gly Tyr 90 Lys Val Ile Asn Val Asp Ser Ser Asp Lys Asp Asp Phe Ser Phe Ala 100 105 110 Gin Lys Lys Glu Gly Tyr Leu Ala Val Ala Met Asn Gly Glu Ile Val 115 120 125 Leu Arg Pro Asp Pro Lys Arg Thr Ile Gin Lys Lys Ser Glu Pro Gly 130 135 140 Leu Leu Phe Ser Thr Gly Leu Asp Lys Met Glu Arg Val Leu Ile Pro 145 150 155 160 Ala Gly Phe Val Lys Val Thr Ile Leu Glu Pro Met Ser Gly Glu Ser 165 170 175 Leu Asp Ser Phe Thr Met Asp Leu Ser Glu Leu Asp Ile Gin Glu Lys 180 185 190 Phe Leu Lys Thr Thr His Ser Ser His Ser Gly Gly Leu Val Ser Thr 195 200 205 Met Val Lys Gly Thr Asp Asn Ser Asn Asp Ala Ile Lys Ser Ala Leu 210 215 220 Asn Lys Ile Phe Ala Ser Ile Met Gin Glu Met Asp Lys Lys Leu Thr 225 230 235 240 Gin Arg Asn Leu Glu Ser Tyr Gin Lys Asp Ala Lys Glu Leu Lys Asn 245 250 255 Lys Arg Asn Arg 260 INFORMATION FOR SEQ ID NO:131: SEQUENCE CHARACTERISTICS: LENGTH: 1382 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...1382 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:131: Leu Asn Phe Asn Asn Leu Thr Ala Asn Gly Ala Leu Asn Phe Asn Gly WO 98/18323 PCT/US97/19575 209

I

Tyr Val Asp Gly Tyr Gin Giu Asn Tyr 145 Asp Phe Pro Ser Ala 225 Asn Ala Ile Asp Tyr 305 Asn Tyr Ile Phe Gin 385 Lys Met Ala Al a Leu Asn Ile Gly Thr Ser Ser 130 Gin Asn Thr Phe Ser 210 Thr Ile Gin Asn Asn 290 Ser Thr Ile Gly Gin 370 Ala Ile Giu Leu Pro Giy 35 Ile Thr Met Trp Ile Ala Asp Gin Pro Asn 195 Giu Leu Asn Lys Gin 275 Val Ser Tyr Asn Ser 355 Ser Thr Phe Lys Ser 435 Ser Asn Thr Gly Lys Ser 100 Lys Ser Ser Ala Lys 180 Gin Asn Lys Giu Gin 260 Thr Thr Pro Leu Aia 340 Ser Aila Asp Asn Ile 420 Pro Leu Thr Asn Gly Lys Ser Ile Ser 70 Ile Gin Phe Ile Asn Gly Asn Thr Lys Gin 150 Gly Thr 165 Gly Ser Pro Leu Leu Lys Giu Met 230 Val Leu 245 Ala Leu Phe Asn Asn Ser Cys Ala 310 Gly Gin 325 Asp Phe Asn Ala Asn Asn Asn Ile 390 Gin Gly 405 Lys Gin Leu Ser Lys Asp Val 55 Gly Asn Asn Asp Ile i3 5 Asn Tyr Gin Asn Thr 215 Ile Gin Leu Asn Thr 295 Leu Leu Lys Phe Leu 375 Phe Asn Aia Lys Al a Ile Thr Ala Al a Pro Leu 120 Phe Pro Tyr Thr Ser 200 Leu Giu Leu Glu Gly 280 Ser Asp Leu Aia Giu 360 Val Asn Leu Gly Giu 440 Leu 25 Asn Tyr Asn Thr Leu 105 Thr Asn Thr Leu Pro 185 Leu Leu Ser Leu Thr 265 Asn Ser Ser Gly Lys 345 Ser Leu Leu Ala Giy 425 Leu 10 Met Leu Asn Gly Tyr 90 Asn Ile Ile Giy Thr 170 Gin Asn Gly Asn Asp 250 Ile Leu Ile Ala Ser 330 Ser Gly Asn Leu Asn 410 Leu Pro Asn Val Ser Asp Ile Leu Tyr Giu 75 Ser Asp Ser Ser Giu Vai Ala Pro 140 Tyr Ser 155 Ser Asn Thr Pro Ile Tyr Ile Leu 220 Gin Leu 235 Lys Ile Asn His Val Ile Trp Phe 300 Thr Cys 315 Thr Ser Ile Tyr Gly Ser Lys Ala 380 Gly Gin 395 Vai Leu Gly Asn Ala Ser Giy Asn Ala Ile Asn Ile Asn Leu Asp Lys Thr 190 Lys Gin Asn Ile Thr 270 Aia Gly Ser Tyr Thr 350 Asp Ile Gly Gin Ile 430 Gin Gin Ile Gin Leu Asn Ile Asn Tyr Tyr Giy 175 Tyr Gly Asn Ile Thr 255 Asp Thr Asn Phe Leu 335 Gly Val Glu Ile Met 415 Giu Asp Phe Phe Lys Phe Ile Gin Pro Asn Ser 160 Leu Ser Phe Ser Thr 240 Gin Asn Gin Giy Arg 320 Gly Thr Thr Ala Asp 400 Al a Asn Glu WO 98/18323 PCTIUS97/19575 -210- Thr Leu Gly Gin Leu Ile Gly Gin Asn Asn Leu Asp Asp Leu Leu Asn 450 455 460 Asn Ser Gly Val Met Asn Giu Ile Gin Asn Ile Ile Ser Gin Lys Leu 465 470 475 480 Ser Ile Phe Gly Asn Phe Vai Thr Pro Ser Ile Ile Giu Asn Tyr Leu 485 490 495 Aia Lys Gin Ser Leu Lys Ser Met Leu Asp Asp Lys Giy Leu Leu Asn 500 505 510 Phe Ile Giy Giy Tyr Ile Asp Aia Ser Giu Leu Ser Ser Ile Leu Giy 515 520 525 Vai Ile Leu Lys Asp Ile Thr Asn Pro Pro Thr Ser Leu Gin Lys Asp 530 535 540 Ile Gly Val Val Ala Asn Asp Leu Leu Asn Giu Phe Leu Gly Gin Asp 545 550 555 560 Vai Val Lys Lys Leu Giu Ser Gin Giy Leu Val Ser Asn Ile Ile Asn 565 570 575 Asn Vai Ile Ser Gin Gly Gly Leu Ser Giy Vai Tyr Asn Gin Gly Leu 580 585 590 Giy Ser Val Leu Pro Pro Ser Leu Gin Asn Ala Leu Lys Giu Asn Asp 595 600 605 Leu Giy Thr Leu Leu Ser Pro Arg Gly Leu His Asp Phe Trp Gin Lys 610 615 620 Gly Tyr Phe Asn Phe Leu Ser Asn Gly Tyr Val Phe Val Asn Asn Ser 625 630 635 640 Ser Phe Ser Asn Ala Thr Gly Gly Ser Leu Asn Phe Vai Ala Asn Lys 645 650 655 Ser Ile Ile Phe Asn Giy Asp Asn Thr Ile Asp Phe Ser Lys Tyr Gin 660 665 670 Gly Ala Leu Ile Phe Ala Ser Asn Gly Val Ser Asn Ile Asn Ile Thr 675 680 685 Thr Leu Asn Ala Thr Asn Gly Leu Ser Leu Asn Ala Gly Leu Asn Asn 690 695 700 Vai Ser Val Gin Lys Gly Glu Ile Cys Ile Asn Leu Aia Asn Cys Pro 705 710 715 720 Thr Thr Lys Asn Ser Ser Pro Ala Asn Ser Ser Val Thr Pro Thr Asn 725 730 735 Giu Ser Leu Ser Vai His Ala Asn Asn Phe Thr Phe Leu Giy Thr Ile 740 745 750 Ile Ser Asn Giy Ala Ile Asp Leu Ser Gin Val Thr Asn Asn Ser Val 755 760 765 Ile Gly Thr Leu Asn Leu Asn Giu Asn Ala Thr Leu Gin Aia Asn Asn 770 775 780 Leu Thr Ile Thr Asn Ala Phe Asn Asn Aia Ser Asn Ser Thr Ala Asn 785 790 795 800 Ile Asp Giy Asn Phe Thr Leu Asn Gin Gin Ala Thr Leu Ser Thr Asn 805 810 815 Ala Ser Giy Leu Asn Val Met Gly Asn Phe Asn Ser Tyr Gly Asp Leu 820 825 830 Val Phe Asn Leu Ser His Ser Val Ser His Ala Ile Ile Asn Thr Gin 835 840 845 Giy Thr Ala Thr Ile Met Ala Asn Asn Asn Pro Leu Ile Gin Phe Asn 850 855 860 Ala Ser Ser Lys Giu Val Gly Thr Tyr Thr Leu Ile Asp Ser Ala Lys 865 870 875 880 Ala Ile Tyr Tyr Gly Tyr Asn Asn Gin Ile Thr Gly Gly Ser Ser Leu WO 98/18323 PCT/US97/19575 -211- 885 890 895 Asp Asn Tyr Leu Lys Leu Tyr Ala Leu Ile Asp Ile Asn Gly Lys His 900 905 910 Met Val Met Thr Asp Asn Gly Leu Thr Tyr Asn Gly Gin Ala Val Ser 915 920 925 Val Lys Asp Gly Gly Leu Val Val Gly Phe Lys Asp Ser Gin Asn Gin 930 935 940 Tyr Ile Tyr Thr Ser Ile Leu Tyr Asn Lys Val Lys Ile Ala Val Ser 945 950 955 960 Asn Asp Pro Ile Asn Asn Pro Gin Ala Pro Thr Leu Lys Gin Tyr Ile 965 970 975 Ala Gin Ile Gin Gly Val Gin Ser Val Asp Ser Ile Asp Gin Ala Gly 980 985 990 Gly Asn Gin Ala Ile Asn Trp Leu Asn Lys Ile Phe Glu Thr Lys Gly 995 1000 1005 Ser Pro Leu Phe Ala Pro Tyr Tyr Leu Glu Ser His Ser Thr Lys Asp 1010 1015 1020 Leu Thr Thr Ile Ala Gly Asp Ile Ala Asn Thr Leu Glu Val Ile Ala 1025 1030 1035 1040 Asn Pro Asn Phe Lys Asn Asp Ala Thr Asn Ile Leu Gin Ile Asn Thr 1045 1050 1055 Tyr Thr Gin Gin Met Ser Arg Leu Ala Lys Leu Ser Asp Thr Ser Thr 1060 1065 1070 Phe Ala Arg Ser Asp Phe Leu Glu Arg Leu Glu Ala Leu Lys Asn Lys 1075 1080 1085 Arg Phe Ala Asp Ala Ile Pro Asn Ala Met Asp Val Ile Leu Lys Tyr 1090 1095 1100 Ser Gin Arg Asn Arg Val Lys Asn Asn Val Trp Ala Thr Gly Val Gly 1105 1110 1115 1120 Gly Ala Ser Phe Ile Ser Gly Gly Thr Gly Thr Leu Tyr Gly Ile Asn 1125 1130 1135 Val Gly Tyr Asp Arg Phe Ile Lys Gly Val Ile Val Gly Gly Tyr Ala 1140 1145 1150 Ala Tyr Gly Tyr Ser Gly Phe His Ala Asn Ile Thr Gin Ser Gly Ser 1155 1160 1165 Ser Asn Val Asn Val Gly Val Tyr Ser Arg Ala Phe Ile Lys Arg Ser 1170 1175 1180 Glu Leu Thr Met Ser Leu Asn Glu Thr Trp Gly Tyr Asn Lys Thr Phe 1185 1190 1195 1200 Ile Asn Ser Tyr Asp Pro Leu Leu Ser Ile Ile Asn Gin Ser Tyr Arg 1205 1210 1215 Tyr Asp Thr Trp Thr Thr Asp Ala Lys Ile Asn Tyr Gly Tyr Asp Phe 1220 1225 1230 Met Phe Lys Asp Lys Ser Val Ile Phe Lys Pro Gin Val Gly Leu Ser 1235 1240 1245 Tyr Tyr Tyr Ile Gly Leu Ser Gly Leu Arg Gly Ile Met Asp Asp Pro 1250 1255 1260 Ile Tyr Asn Gin Phe Arg Ala Asn Ala Asp Pro Asn Lys Lys Ser Val 1265 1270 1275 1280 Leu Thr Ile Asn Phe Ala Leu Glu Ser Arg His Tyr Phe Asn Lys Asn 1285 1290 1295 Ser Tyr Tyr Phe Val Ile Ala Asp Val Gly Arg Asp Leu Phe Ile Asn 1300 1305 1310 Ser Met Gly Asp Lys Met Val Arg Phe Ile Gly Asn Asn Thr Leu Ser 1315 1320 1325 WO 98/18323 PCT/US97/19575 -212- Tyr Arg Asp Gly Gly Arg Tyr Asn-Thr Phe Ala Ser Ile Ile Thr Gly 1330 1335 1340 Gly Glu Ile Arg Leu Phe Lys Thr Phe Tyr Val Asn Ala Gly Ile Gly 1345 1350 1355 1360 Ala Arg Phe Gly Leu Asp Tyr Lys Asp Ile Asn Ile Thr Gly Asn Ile 1365 1370 1375 Gly Met Arg Tyr Ala Phe 1380 INFORMATION FOR SEQ ID NO:132: SEQUENCE CHARACTERISTICS: LENGTH: 262 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...262 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132: Met Lys Lys Ile Gly Leu Ser Leu Cys Leu Val Leu Ser Leu Gly Phe 1 5 10 Leu Lys Ala His Glu Val Ser Ala Glu Glu Ile Ala Asp Ile Phe Tyr 25 Lys Leu Asn Ala Lys Glu Pro Lys Met Lys Ile Asn His Thr Lys Gly 35 40 Phe Cys Ala Lys Gly Val Phe Leu Pro Asn Pro Gin Ala Arg Glu Asp 55 Leu Glu Val Pro Leu Leu Asn Glu Lys Glu Ile Pro Ala Ser Val Arg 70 75 Tyr Ser Leu Gly Gly Val Ala Met Asp Asp Lys Ser Lys Val Arg Gly 90 Met Ala Leu Lys Leu Glu Asn Gin Asn Ala Ser Trp Thr Met Val Met 100 105 110 Leu Asn Thr Glu Ile Asn Phe Ala Lys Asn Pro Glu Glu Phe Ala Gin 115 120 125 Phe Phe Glu Met Arg Leu Pro Lys Asn Gly Lys Val Asp Glu Ala Arg 130 135 140 Ile Lys Lys Leu Tyr Glu Glu Val Pro Ser Tyr Arg Asn Phe Ala Ala 145 150 155 160 Tyr Met Lys Thr Ile Gly Ile Ser Ser Ser Val Ala Asn Thr Pro Tyr 165 170 175 Tyr Ser Val His Ala Phe Lys Phe Lys Asp Lys Lys Glu Lys Leu Leu 180 185 190 Pro Ala Arg Trp Lys Phe Val Pro Lys Glu Gly Val Lys Tyr Leu Asn D 195 200 205 WO 98/18323 WO 9818323PCTfUS97/19575 -213- Pro Gin Giu Leu Lys Gin Lys Asp Ser Asn Tyr Leu Leu Ser Ser Phe 210 215 220 Gin Gin His Leu Lys Asn Lys Pro Ile Giu Tyr Gin Met Tyr Leu Vai 225 230 235 240 Phe Aia Asn Gin Asn Asp Ala Thr Asn Asp Thr Thr Ala Leu Trp, Lys 245 250 255 Gly Ser Ile Arg Asn Tyr 260 INFORMATION FOR SEQ ID NO:133: SEQUENCE CHARACTERISTICS: LENGTH: 246 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .246 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i33: Met Lys Gin Phe Lys Lys Lys Pro Lys Lys Ile Lys 1 Asn Ile Giy Trp Phe Aia Lys Gly Ala 145 Tyr Val Gin Gly Leu Tyr Thr Asn Asn Gly 130 Thr Pro Asn Lys Giy 35 Ser Ala Gly Tyr Asp 115 Giu Phe Asn Asn Thr Phe Trp Ile Asn Tyr 100 Asn Tyr Asn Gly Ser 180 5 Ile Ala Gly Trp Gin His Giy Asn Leu His 165 Val Leu Ser Giu Ser 70 Leu Sen Thr Giy Gly 150 Thr Glu Lys Gly Lys 55 Cys Ile Gin Tyr Gly 135 Ala Asp Val1 Arg Val 40 Ser Asp Thr Asn Phe 120 Asn Ser Vai Gly Pro 25 Tyr Gin Lys Lys Asn 105 Leu Leu Ser Thr Asn 185 Trp Asp Val Giu Trp Asp Gly Ile Asn 155 Ser Val Leu Gly Cys Giu Ala Ile Leu Giu 140 Ser Al a Gly Ang Met Thr Vai Lys Gly Thr Tyr 125 Leu Phe Gly Ser Sen Pro Asp His Thr Gly Ala 110 Asn Gly Thr Thr Gly 190 His Leu Ile Arg Gin Asn Asn Tyr Ser Ser Ile 175 Ala Thr His Thr Gly Thr Ala Thr Leu Asn Leu Asn Ala Asn Lys Val Thr 195 200 ?c WO 98/18323 PCT/US97/19575 -214- Ile Asn Ser Asn Ile Ser Ala Tyr Lys Thr Ser Gin Val Asn Val Gly 210 215 220 Asn Ala Asn Ser Val Ile Thr Ile Asn Ser Val Ser Leu Asn Gly Glu 225 230 235 240 Tyr Leu Gin Phe Phe Ser 245 INFORMATION FOR SEQ ID NO:134: SEQUENCE CHARACTERISTICS: LENGTH: 245 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...245 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134: Met Ile Lys Lys Thr Leu Ala Ser Val Leu Leu Gly Leu Ser Leu Met 1 5 10 Ser Val Leu Asn Ala Lys Glu Cys Val Ser Pro Ile Thr Arg Ser Val 25 Lys Tyr His Gin Gin Ser Ala Glu Ile Arg Ala Leu Gin Leu Gin Ser 40 Tyr Lys Met Ala Lys Met Ala Leu Asp Asn Asn Leu Lys Leu Val Lys 50 55 Asp Lys Lys Pro Ala Val Ile Leu Asp Leu Asp Glu Thr Val Leu Asn 70 75 Thr Phe Asp Tyr Ala Gly Tyr Leu Val Lys Asn Cys Ile Lys Tyr Thr 90 Pro Glu Thr Trp Asp Lys Phe Glu Lys Glu Gly Ser Leu Thr Leu Ile 100 105 110 Pro Gly Ala Leu Asp Phe Leu Glu Tyr Ala Asn Ser Lys Gly Val Lys 115 120 125 Ile Phe Tyr Ile Ser Asn Arg Thr Gin Lys Asn Lys Ala Phe Thr Leu 130 135 140 Lys Thr Leu Lys Ser Phe Lys Leu Pro Gin Val Ser Glu Glu Ser Val 145 150 155 160 Leu Leu Lys Glu Lys Gly Lys Pro Lys Ala Val Arg Arg Glu Leu Val 165 170 175 Ala Lys Asp Tyr Ala Ile Val Leu Gin Val Gly Asp Thr Leu His Asp 180 185 190 Phe Asp Ala Ile Phe Ala Lys Asp Ala Lys Asn Ser Gin Glu Gin Gin 195 200 205 Ala Lys Val Leu Gin Asn Ala Gin Lys Phe Gly Thr Glu Trp Ile Ile 210 215 220 WO 98/18323 WO 9818323PCTIUS97/19575 -215- Leu Pro Asn Ser Leu Tyr Gly Thr Trp Glu Asp Gly Pro Ile Lys Ala 225 230 235 240 Trp Gin Asn Lys Lys INFORMATION FOR SEQ ID NO:135: SEQUENCE CHARACTERISTICS: LENGTH: 288 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION i1 .288 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135: Leu Trp Cys Leu Lys Thr Pro Ile Ile Gly His Giy 1 Aia Ala Gin Lys 65 Leu Thr Gly Glu Gly 145 Lys Trp Leu Tyr Val Phe Phe Ser Asn Thr Gly Tyr Trp Lys Val Met 195 Pro Phe Phe Asp Ala Tyr Lys 100 Leu Glu Val Asn Asn 180 Trp, Tyr 5 Trp Leu Lys Lys Asp Giu Leu Ile Sen Met 165 Ala Asn Ile Cys Leu Gin Asp 70 Val Ala Val Ile Al a 150 Ser Thr Pro Phe Cys Ser Asn Asn Tyr Leu Lys Phe 135 Asp Ala Sen Lys Met 215 Phe Val 40 His Val1 Ile Leu Thr 120 Pro Ile Ser Gly Ile 200 Ser 10 Met Asp Ile Thr Ala 90 Gly Tyr Tyr Ser Cys 170 Phe Val Ser Ile Ala Phe Ala 75 Asp Asn Val1 Val Gly 1-55 Ser Asn Gly Asn Arg Lys Giu Ser Lys Ile Lys Gin 140 Lys Ile Met Asp Lys 220 Met Tnp Glu Ile Gly Val Lys Leu 125 Asp Asp Asp Gin Ile 205 Arg Lys Leu Ile Leu Asn Arg Val 110 Ser Ser Gin Asn Lys 190 Pro Thr Lys is Tyr Ala Ala Ala Tyr Tyr Leu Val Lys Pro 175 Ser Val Thr Lys Leu Met Asp Ile Asp Arg Asn Sen Tyr 160 Ile His Leu Gly Phe Leu Tyr Pro Glu Phe Gly Thn Sen Asn Leu Asp Gly Phe Ile Tyr 225 230 235 240 WO.98/18323 PCT/US97/19575 -216- Leu Gin Pro Phe Tyr Leu Ala Pro Lys Asn Ser Trp Asp Met Thr Phe 245 250 255 Thr Pro Gin Ile Arg Tyr Lys Arg Gly Phe Gly Leu Asn Phe Glu Ala 260 265 270 Arg Tyr Ile Asn Ser Lys Thr Gin Val Phe Ile Gin Cys Ala Leu Phe 275 280 285 INFORMATION FOR SEQ ID NO:136: SEQUENCE CHARACTERISTICS: LENGTH: 128 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...128 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136: Leu Met Phe Lys Lys Met Cys Leu Ser Leu Leu Met Ile Ser Gly Val 1 5 10 Cys Val Gly Ala Lys Asp Leu Asp Phe Lys Leu Asp Tyr Arg Ala Thr 25 Gly Gly Lys Phe Met Gly Lys Met Thr Asp Ser Ser Leu Leu Ser Ile 40 Thr Ser Met Asn Asp Glu Pro Val Val Ile Lys Asn Leu Ile Val Asn 50 55 Arg Gly Asn Ser Cys Glu Ala Thr Lys Lys Val Glu Pro Lys Phe Gly 70 75 Asp Lys Phe Lys Lys Glu Lys Leu Phe Asp His Glu Leu Lys Tyr Ser 90 Gin Gin Ile Phe Tyr Arg Leu Asp Cys Lys Pro Asn Gin Leu Leu Glu 100 105 110 Val Lys Ile Ile Thr Asp Lys Gly Glu Tyr Tyr His Lys Phe Ser Lys 115 120 125 INFORMATION FOR SEQ ID NO:137: SEQUENCE CHARACTERISTICS: LENGTH: 169 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES WO 98/18323 PCT/US97/19575 -217- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...169 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137: Met Gin Ala Leu Lys Ser Leu Leu Glu Val Ile Thr Lys Leu Gin Asn 1 5 10 Leu Gly Gly Tyr Leu Met His Ile Ala Ile Phe Ile Ile Phe Ile Trp 25 Ile Gly Gly Leu Lys Phe Val Pro Tyr Glu Ala Glu Gly Ile Ala Pro 35 40 Phe Val Ala Asn Ser Pro Phe Phe Ser Phe Met Tyr Lys Phe Glu Lys 55 Pro Ala Tyr Lys Gin His Lys Met Ser Glu Ser Gin Ser Met Gin Glu 70 75 Glu Met Gin Asp Asn Pro Lys Ile Val Glu Asn Lys Glu Trp His Lys 90 Glu Asn Arg Thr Tyr Leu Val Ala Glu Gly Leu Gly Ile Thr Ile Met 100 105 110 Ile Leu Gly Ile Leu Val Leu Leu Gly Leu Trp Met Pro Leu Met Gly 115 120 125 Val Val Gly Gly Leu Leu Val Ala Gly Met Thr Ile Thr Thr Leu Phe 130 135 140 Phe Phe Ile His Asn Ala Arg Ser Val Cys Gin Ser Ala Phe Pro Met 145 150 155 160 Ala Phe Trp Gly Trp Lys Ala Ser Gly 165 INFORMATION FOR SEQ ID NO:138: SEQUENCE CHARACTERISTICS: LENGTH: 487 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...487 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138: Met Ile Glu Trp Met Gin Asn His Arg Lys Tyr Leu Val Val Thr Ile 1 5 10 Trp Ile Ser Thr Ile Ala Phe Ile Ala Ala Gly Met Ile Gly Trp Gly .r WO 98/18323 PCT/US97/19575 -218- Gin Ile Asp Gin Asn Thr Lys Ser 145 Ile Glu Ile Glu Thr 225 Thr Tyr Gin Arg Gin 305 Lys Lys Leu Gin Lys 385 Gly Thr Lys Ser Tyr Lys 50 Ala Ile Gin Lys Asp 130 His Leu Gin Leu Met 210 Ser Asp Leu Vai Ser 290 Asp Leu Asp Gin Glu 370 Asp Thr Leu Vai Ala 450 Ser Ile Tyr Lys Ala Gin 115 Gly Tyr Gin Ser Ile 195 Lys Phe Leu Asp Lys 275 Tyr Phe Thr Gly Asn 355 Lys Phe Ile Phe Val 435 Glu Phe Ser Ala Ala Leu 100 Glu Val Arg Lys Ser 180 Leu Lys Lys Lys Lys 260 His Ile Glu Ala Phe 340 Phe Thr Lys Ser Asn 420 Leu Glu Ser Gin Glu Met Leu Val Phe Pro Ile 165 Leu Asn Tyr Thr Glu 245 Glu Asp Ala Lys Leu 325 Ile Asp Leu Gly Glu 405 Arg Tyr Asn Leu Glu Ser 70 His Arg Ala Asp Lys 150 Ser Ser Pro Tyr Arg 230 Leu Gly Leu Leu Asn 310 Lys Val Glu Met Lys 390 Leu Gin Gin Gin Asp Glu 55 Ile Leu Asn Lys Glu 135 His Ala Leu Asn Glu 215 Ser Glu Lys Asn Lys 295 Asn Pro Vai Ala Ala 375 Ser Asn Glu Ile Tyr 455 Ser 40 Leu Pro Glu Phe Glu 120 Glu Phe Leu Trp Asp 200 Asn Leu Glu Leu Met 280 Lys Ser Leu Gin Lys 360 Leu Val Gin Lys Thr 440 Met 25 Asp Ala Asp Lys Ala 105 Ile Leu Glu Phe Ala 185 Val His Tyr Tyr Gin 265 Gin Gly Pro Glu Leu 345 Ser Gin Gly Glu Lys 425 Glu Gin Ser Gin Phe Ser 90 Leu Arg Tyr Glu Pro 170 Lys Lys Arg Phe Tyr 250 Asp Lys Asn Tyr Val 330 Val Ala Thr Tyr Glu 410 Gly Gin Arg Ala Glu Lys 75 Ala Asp Lys Lys Ser 155 Lys Leu lie Lys Asp 235 His Phe Ala Ala Thr 315 Leu Ser Leu Leu Val 395 Ser Phe Asn Leu Ala Tyr Glu Leu Leu Thr Asn 140 Val Thr Gin Ser Asp 220 Ala Lys Lys Asn Gin 300 Ala Lys Gin Lys Ala 380 Ser Ala Val Phe Val 460 Lys Vai Arg Arg Leu Thr Asp Ser Gly Leu 110 Asn Val 125 Ile Leu Glu Arg Thr Thr Asp Lys 190 Leu Asn 205 Phe Lys Ser Leu Asn Lys Ser Val 270 Glu Lys 285 Asn Tyr Glu Ile Pro Glu Ile Lys 350 Thr Arg 365 Lys Glu Pro Asn Lys Phe Thr Ile 430 Asn His 445 Asn Asn Gly Leu Glu Leu Gly Phe Lys Leu Pro 175 Leu Glu Lys Glu Val 255 Gin Ala Thr Thr Pro 335 Asp Leu Lys Phe Ile 415 Gly Pro Thr Gin Lys Asp Ile Ala Gin Gin Leu 160 Leu Asp Glu Pro Lys 240 Ser Glu Leu Thr Gln 320 Phe Glu Thr Leu Gly 400 Asn Asn Phe Lys WO98/18323 PCT/US97/19575 -219- Thr Asp Phe Phe Asp Lys Ala Leu Ile Glu Glu Leu Lys Lys Arg Tyr 465 470 475 480 Lys Ile Val Lys Tyr Ile Gin 485 INFORMATION FOR SEQ ID NO:139: SEQUENCE CHARACTERISTICS: LENGTH: 142 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...142 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139: Met Lys Thr Asn Phe Tyr Lys Ile Lys Leu Leu Phe Ala Trp Cys Leu 1 5 10 Ile Ile Gly Met Phe Asn Ala Pro Leu Asn Ala Asp Gin Asn Thr Asp 25 Ile Lys Asp Ile Ser Pro Glu Asp Met Ala Leu Asn Ser Val Gly Leu 40 Val Ser Arg Asp Gin Leu Lys Ile Glu Ile Pro Lys Glu Thr Leu Glu 55 Gin Lys Val Ala Ile Leu Asn Asp Tyr Asn Asp Lys Asn Val Asn Ile 65 70 75 Lys Phe Asp Asp Ile Ser Leu Gly Ser Phe Gin Pro Asn Asp Asn Leu 90 Gly Ile Asn Ala Met Trp Gly Ile Gin Asn Leu Leu Met Ser Gin Met 100 105 110 Met Ser Asn Tyr Gly Pro Asn Asn Ser Phe Met Tyr Gly Tyr Ala Pro 115 120 125 Thr Tyr Ser Asp Ser Ser Phe Leu Pro Pro Ile Leu Gly Tyr 130 135 140 INFORMATION FOR SEQ ID NO:140: SEQUENCE CHARACTERISTICS: LENGTH: 208 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES WO 98/18323 PCT/US97/19575 -220- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...208 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140: Leu Ile Asn Asn Asn Asn Asn Asn Lys Lys Leu Arg Gly Phe Phe Leu 1 5 10 Lys Val Leu Leu Ser Leu Val Val Phe Ser Ser Tyr Gly Ser Ala Asn 25 Asp Asp Lys Glu Ala Lys Lys Glu Ala Leu Glu Lys Glu Lys Asn Thr 35 40 Pro Asn Gly Leu Val Tyr Thr Asn Leu Asp Phe Asp Ser Phe Lys Ala 55 Thr Ile Lys Asn Leu Lys Asp Lys Lys Val Thr Phe Lys Glu Val Asn 70 75 Pro Asp Ile Ile Lys Asp Glu Val Phe Asp Phe Val Ile Val Asn Arg 90 Val Leu Lys Lys Ile Lys Asp Leu Lys His Tyr Asp Pro Val Ile Glu 100 105 110 Lys Ile Phe Asp Glu Lys Gly Lys Glu Met Gly Leu Asn Val Glu Leu 115 120 125 Gin Ile Asn Pro Glu Val Lys Asp Phe Phe Thr Phe Lys Ser Ile Ser 130 135 140 Thr Thr Asn Lys Gin Arg Cys Phe Leu Ser Leu His Gly Glu Thr Arg 145 150 155 160 Glu Ile Leu Cys Asp Asp Lys Leu Tyr Asn Val Leu Leu Ala Val Phe 165 170 175 Asn Ser Tyr Asp Pro Asn Asp Leu Leu Lys His Ile Ser Thr Ile Glu 180 185 190 Ser Leu Lys Lys Ile Phe Tyr Thr Ile Thr Cys Glu Ala Val Tyr Leu 195 200 205 INFORMATION FOR SEQ ID NO:141: SEQUENCE CHARACTERISTICS: LENGTH: 245 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...245 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141: WO 98/18323 PCT/US97/19575 -221- Met 1 Ser Phe Val Asn Gin Val Ala Ile Ile 145 Thr Pro Asn Leu Ile 225 Thr Ala Gin Ala Val Gin Gin Gly Gin Ala 130 Glu Val Lys Ser Gly 210 Ser Ser Gly Val Gly Gly Ser Tyr Asn Gly 115 Ser Ala Glu Tyr Ser 195 Ala Met Gly Thr Ser 20 Ile Phe Ile Asn Asn 100 Asn Ile Tyr Met Ala 180 Met Leu Thr Cys Gin 5 Ser Val Thr Ala Gin Ile Thr Leu Ala Met 165 Leu Asn Val Pro His 245 Ala Ile Ala Asn Glu 70 Leu Leu Gin Ala Thr 150 Ser Ala Asp Gly Met 230 Ile Ile Gly Pro 55 Ala Tyr Asn Ser Ser 135 Asn Gly Leu Thr Ser 215 Ser Tyr Ser Ala 40 Gin Val Gin Ile Ala 120 Asn Gin Ile Gin Ala 200 Ser Glu Ser 25 Met Met Ser Gly Ser 105 Gin Thr Ile Leu Glu 185 Asp Lys Ser 10 Thr Thr Thr Val Phe 90 Lys Ile Thr Ala Gly 170 Gin Ser Val Ser Ser Ala Ala Pro 75 Asn Leu Ser Pro Val 155 Asn Leu Leu Phe Ser Gly Ala Ile Met Asp Thr Ala Lys 140 Pro Ile Arg Asp Phe 220 Ala Val Ile Met Lys Gin Gly Val 125 Asn Ser Thr Ser Ser 205 Ser Gly Ala Ile Thr Ala Ser Glu 110 Asn Pro Val Ser Gin 190 Cys Cys Phe Gly Pro Gin Ala Met Phe Ser Ser Pro Ala 175 Ala Thr Met Leu Pro Ile Tyr Asn Ala Asn Gin Ala Thr 160 Ala Ser Ala Gin Val Ser Met Pro Thr Val Met Pro Asn 235 240 INFORMATION FOR SEQ ID NO:142: SEQUENCE CHARACTERISTICS: LENGTH: 367 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...367 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142: Met Ile Lys Ser Val Glu Ile Glu Asn Tyr Lys Asn Phe Glu His Leu WO 98/18323 PCT/US97/19575 -222- 1 5 10 Lys Met Glu Asn Phe Lys Leu Ile Asn Phe Phe Thr Gly Gin Asn Asp 25 Ala Gly Lys Thr Asn Leu Leu Glu Ala Leu Tyr Thr Asn Thr Gly Leu 35 40 Cys Asp Pro Thr Ala Asn Gin Val Ser Leu Pro Pro Glu His Ala Val 55 Asn Ile Ser Glu Phe Arg Lys Ile Lys Leu Asp Ala Asp Asn Leu Lys 70 75 Thr Phe Phe Tyr Gin Gly Asn Thr Ala Asn Pro Ile Ser Ile Arg Thr 90 Glu Phe Glu His Ala Thr Ile Pro Leu Thr Ile Gin Tyr Pro Thr Gin 100 105 110 Thr Ser Tyr Ser Lys Asp Ile Asn Leu Asn Ser Asp Asp Ala His Met 115 120 125 Thr Asn Leu Ile Asn Thr Thr Ile Thr Lys Pro Gin Leu Gin Phe Ser 130 135 140 Tyr Asn Pro Ser Leu Ser Pro Met Thr Met Thr Tyr Glu Phe Glu Arg 145 150 155 160 Gin Asn Leu Gly Leu Ile His Ser Asn Leu Asp Lys Ile Ala Gin Thr 165 170 175 Tyr Lys Glu Asn Ala Met Phe Ile Pro Ile Glu Leu Ser Ile Val Asn 180 185 190 Ser Leu Lys Ala Leu Glu Asn Leu Gin Leu Ala Ser Lys Glu Lys Glu 195 200 205 Leu Ile Glu Ile Leu Gin Cys Phe Asn Pro Asn Ile Leu Asn Ala Asn 210 215 220 Thr Ile Arg Lys Ser Val Tyr Ile Gin Ile Lys Asp Glu Asn Thr Pro 225 230 235 240 Leu Glu Glu Ser Pro Lys Arg Leu Leu Asn Leu Phe Gly Trp Gly Phe 245 250 255 Ile Lys Phe Phe Ile Met Val Ser Ile Leu Ile Asp Asn Arg Val Lys 260 265 270 Tyr Leu Phe Ile Asp Glu Ile Glu Ser Gly Leu His His Thr Lys Met 275 280 285 Gin Glu Phe Leu Lys Ala Leu Phe Lys Leu Ala Gin Lys Leu Gin Ile 290 295 300 Gin Ile Phe Ala Thr Thr His Asn Lys Glu Phe Leu Leu Asn Ala Ile 305 310 315 320 Asn Thr Ile Ser Asp Asn Glu Thr Gly Val Phe Lys Asp Ile Ala Leu 325 330 335 Phe Glu Leu Glu Lys Glu Ser Ala Ser Gly Phe Ile Arg His Ser Tyr 340 345 350 Ser Met Leu Glu Lys Ala Leu Tyr Arg Gly Met Glu Val Arg Gly 355 360 365 INFORMATION FOR SEQ ID NO:143: SEQUENCE CHARACTERISTICS: LENGTH: 409 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/18323 PCT/US97/19575 -223- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...409 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143: Met Ser Leu Ile Arg Val Asn Gly Glu Ala Phe Lys Leu Ser Leu Glu 1 5 10 Ser Leu Glu Glu Asp Pro Phe Glu Thr Lys Glu Thr Leu Glu Thr Leu 20 25 Glu Thr Leu Ile Lys Gin Thr Ser Val Val Leu Leu Ala Ala Gly Glu 40 Ser Lys Arg Phe Ser Arg Ala Ile Lys Lys Gin Trp Leu Arg Ser His 55 His Thr Pro Leu Trp Leu Ser Val Tyr Glu Ser Phe Lys Glu Ala Leu 70 75 Asp Phe Lys Glu Val Ile Leu Val Val Ser Glu Leu Asp Tyr Val Tyr 90 Ile Gin Arg His Tyr Pro Lys Ile Lys Leu Val Lys Gly Gly Ala Ser 100 105 110 Arg Gin Glu Ser Val Arg Asn Ala Leu Lys Val Ile Asp Ser Thr Tyr 115 120 125 Thr Ile Thr Ser Asp Val Ala Arg Gly Leu Ala Asn Met Glu Ala Leu 130 135 140 Lys Ser Leu Phe Leu Thr Leu Gin Gin Thr Ser His Tyr Cys Ile Ala 145 150 155 160 Pro Tyr Leu Pro Cys Tyr Asp Thr Ala Ile Tyr Tyr Asn Glu Ala Leu 165 170 175 Asp Arg Glu Ala Ile Lys Leu Ile Gin Thr Pro Gin Leu Ser His Thr 180 185 190 Lys Thr Leu Gin Ser Ala Leu Asn Gin Gly Gly Phe Lys Asp Glu Ser 195 200 205 Ser Ala Ile Leu Gin Ala Phe Pro Asn Ser Val Ser Tyr Ile Glu Gly 210 215 220 Ser Lys Asp Leu His Lys Leu Thr Thr Ser Gly Asp Leu Lys Phe Phe 225 230 235 240 Thr Pro Phe Phe Asn Pro Ala Lys Asp Thr Phe Ile Gly Met Gly Phe 245 250 255 Asp Thr His Ala Phe Ile Lys Asp Lys Pro Met Val Leu Gly Gly Val 260 265 270 Val Leu Asp Cys Glu Phe Gly Leu Lys Ala His Ser Asp Gly Asp Ala 275 280 285 Leu Leu His Ala Val Ile Asp Ala Ile Leu Gly Ala Ile Lys Gly Gly 290 295 300 Asp Ile Gly Glu Trp Phe Pro Asp Asn Asp Pro Lys Tyr Lys Asn Ala 305 310 315 320 Ser Ser Lys Glu Leu Leu Lys Ile Val Leu Asp Phe Ser Gin Ser Ile 325 330 335 Gly Phe Glu Leu Leu Glu Met Gly Ala Thr Ile Phe Ser Glu Ile Pro 340 345 350 WO 98/18323 WO 9818323PCT/1US97/19575 Lys Leu Lys 385 Val1 Ile Thr Pro 355 Gly Leu Glu 370 Met Gly Phe Ser Met Arg Lys Ser Gly 390 Lys 224 Pro Ala Ile Leu Giu Asn Leu Ser Gin Leu 360 365 Gin Ile Ser Leu Lys Ala Thr Thr met Glu 375 380 Lys Gin Giu Gly Leu Leu Val Gin Ala His 395 400 Gin Lys Leu INFORMATION FOR SEQ ID NO:144: SEQUENCE CHARACTERISTICS: LENGTH: 270 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. 270 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144: Met Lys Lys Phe Val Ala Leu Gly Leu Leu Ser Ala 1 Ser Leu Thr Asn Ala Phe Gly Pro Leu 145 Gly Tyr Pro Leu Gly Gly Pro Leu Lys Leu Asn 130 Leu Gly Trp Thr Leu Gin 35 Ser Gly Asn Ser Phe 115 Lys Ala Val1 Lys Tyr 195 Al a Ala Val Gly Gly Leu 100 Asp Ile Asp Ala Glu 180 Cys 5 Giu Arg Val Thr Phe Asp Tyr Gin Ile Ile 165 Gin Asn Gly Leu Gly Asn 70 Gly Met Gly Leu Ile 150 Gly Ile Pro Asp Asn Cys 55 Ile Leu Thr His Asp 135 Asp Gly Ile Asn Gly Ser 40 Pro Asn Asn Sen Ala 120 Met Lys Asn Glu Ala 200 10 Tyr Ile Giy His Gly 90 Trp Leu S er Asn Trp 170 Lys Tyr Ile Tyr Leu Ser Tyr Phe Gly Trp Ala 155 Lys Gly Ser Gly Asn Thr Lys Lys Giy Lys Gly 140 Ser Ser Pro Thr Val Thr Thr Al a Tyr Lys Phe Gin 125 Val Phe Ser Asp Asn 205 Leu Asn Gly Asn Ala Phe Arg 110 Val1 Gly Gly Ala Val 190 Thr Sen Tyr Asp Lys Asn Phe Val1 Tyr Ser Ile Ala 175 Cys Sen WO 98/18323 PCT/US97/19575 -225- Val Ala Phe Gin Val Trp Leu Asn Phe Gly Val Arg Ala Asn Ile Tyr 210 215 220 Lys His Asn Gly Val Glu Phe Gly Val Arg Val Pro Leu Leu Ile Asn 225 230 235 240 Lys Phe Leu Ser Ala Gly Pro Asn Ala Thr Asn Leu Tyr Tyr His Leu 245 250 255 Lys Arg Asp Tyr Ser Leu Tyr Leu Gly Tyr Asn Tyr Thr Phe 260 265 270 INFORMATION FOR SEQ ID NO:145: SEQUENCE CHARACTERISTICS: LENGTH: 438 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...438 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145: Met Ala Tyr Lys Pro Asn Lys Lys Lys Leu Lys Glu Leu Arg Glu Gin 1 5 10 Pro Asn Leu Phe Ser Ile Leu Asp Lys Gly Asp Val Ala Thr Asn Asn 25 Pro Val Glu Glu Ser Asp Lys Ala Asn Lys Ile Gin Glu Pro Leu Pro 35 40 Tyr Val Val Lys Thr Gin Ile Asn Lys Ala Ser Met Ile Ser Arg Asp 55 Pro Ile Glu Trp Ala Lys Tyr Leu Ser Phe Glu Lys Arg Val Tyr Lys 70 75 Asp Asn Ser Lys Glu Asp Val Asn Phe Phe Ala Asn Gly Glu Ile Lys 90 Glu Ser Ser Arg Val Tyr Glu Ala Asn Lys Glu Gly Phe Glu Arg Arg 100 105 110 Ile Thr Lys Arg Tyr Asp Leu Ile Asp Arg Asn Ile Asp Arg Asn Arg 115 120 125 Glu Phe Phe Ile Lys Glu Ile Glu Ile Leu Thr His Thr Asn Ser Leu 130 135 140 Lys Glu Leu Lys Glu Gin Gly Leu Glu Ile Gin Leu Thr His His Asn 145 150 155 160 Glu Thr His Lys Lys Ala Leu Glu Asn Gly Asn Glu Ile Val Lys Glu 165 170 175 Tyr Asp His Leu Lys Asp Ile Tyr Gin Glu Val Glu Arg Thr Lys Asp 180 185 190 Gly Gly Leu Val Arg Glu Ile Ile Pro Ser Ile Ser Ser Ala Glu Tyr 195 200 205 WO.98/18323 WO 9818323PCT/US97/19575 226 Phe Thr 225 Glu Ser Phe Asn Asn 305 Gin Giu Tyr Ile Asp 385 Gly Asn Asn Leu Leu Ala Thr Trp 275 Leu Gly Asn Ala Asn 355 Arg Leu Glu Ile Ile 435 Asn Thr Giu 245 Tyr Met Al a Ile Asp 325 Ala Asp Thr Ser Pro 405 Thr Gin Lys Asn 230 Val1 Tyr His Asn Leu 310 Tyr Lys Gly Asn Leu 390 Asn Asn Ile Leu 215 Asp His Ser Arg Asn 295 Gly Ser Ile Asn Asn 375 Ser Ser Thr Phe Giu Leu Ile 265 Ile Asn Thr Arg Leu 345 Arg Giu Ala Ala Asn 425 Giu Giu Ile 250 Asp Asn Lys Lys Ser 330 Gin Giu Lys Ile Asn 410 Asn Ser Val 235 Leu Lys Giu Ile Glu 315 Al a Lys Ile Al a Ile 395 Asn Ile Ile 220 Lys Glu Asp Asn Lys 300 Glu Leu Tyr Lys Tyr 380 Gin Asn Ile Asn Leu Gin Asn 270 Leu Phe Ser Ser Giu 350 Phe Glu Lys Pro Asn 430 Glu Glu Leu 255 Ala Lys Phe Ala Leu 335 Ser Lys Arg Glu Ile 415 Asn Asn Phe 240 Leu Asn Giu Phe Ile 320 Glu Val Glu Tyr Gly 400 Lys Asp INFORMATION FOR SEQ ID NO:146: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 215 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .215 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i46: Met Gin Ala Leu Lys Sen Leu Leu Giu Val Ile Thr Lys Leu Gin Asn 1 5 10 Leu Gly Gly Tyr Leu Met His Ile Ala Ile Phe Ile Ile Phe Ile Trp 20 25 WO 98/18323 PCT/US97/19575 -227- Ile Gly Gly Leu Lys Phe Val Pro Tyr Glu Ala Glu Gly Ile Ala Pro 40 Phe Val Ala Asn Ser Pro Phe Phe Ser Phe Met Tyr Lys Phe Glu Lys 55 Pro Ala Tyr Lys Gin His Lys Met Ser Glu Ser Gin Ser Met Gin Glu 70 75 Glu Met Gin Asp Asn Pro Lys Ile Val Glu Asn Lys Glu Trp His Lys 90 Glu Asn Arg Thr Tyr Leu Val Ala Glu Gly Leu Gly Ile Thr Ile Met 100 105 110 Ile Leu Gly Ile Leu Val Leu Leu Gly Leu Trp Met Pro Leu Met Gly 115 120 125 Val Val Gly Gly Leu Leu Val Ala Gly Met Thr Ile Thr Thr Leu Ser 130 135 140 Phe Leu Phe Thr Thr Pro Glu Val Phe Val Asn Gin His Phe Pro Trp 145 150 155 160 Leu Ser Gly Ala Gly Arg Leu Val Val Lys Asp Leu Ala Leu Phe Ala 165 170 175 Gly Gly Leu Phe Val Ala Gly Phe Asp Ala Lys Arg Tyr Leu Glu Gly 180 185 190 Lys Gly Phe Cys Leu Met Asp Arg Ser Ser Val Gly Ile Lys Thr Lys 195 200 205 Cys Ser Ser Gly Cys Cys Ser 210 215 INFORMATION FOR SEQ ID NO:147: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147: TATACCATGG TGGGCGCTAA INFORMATION FOR SEQ ID NO:148: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid WO 98/18323 PCT/US97/19575 -228- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:148: ATGAATTCGA GTAAGGATTT TTG 23 INFORMATION FOR SEQ ID NO:149: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:149: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:150: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCT/US97/19575 -229- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:150: TAGAATTCGC ATAACGATCA ATC 23 INFORMATION FOR SEQ ID NO:151: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151: ATATCCATGG TGAGTTTGAT GA 22 INFORMATION FOR SEQ ID NO:152: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/18323 PCT/US97/19575 -230- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:152: ATGAATTCAA TTTTTTATTT TGCCA INFORMATION FOR SEQ ID NO:153: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:153: AATTCCATGG TGGGGGCTAT G 21 INFORMATION FOR SEQ ID NO:154: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 WO 98/18323 PCT/US97/19575 -231- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:154: ATGAATTCTC GATAGCCAAA ATC 23 INFORMATION FOR SEQ ID NO:155: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:155: AATTCCATGG TGCATAACTT CCATT INFORMATION FOR SEQ ID NO:156: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:156: AAGAATTCTC TAGCATCCAA ATGGA WO 98/18323 PCT/US97/19575 -232- INFORMATION FOR SEQ ID NO:157: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:157: ATTTCCATGG TCATGTCTCA TATT 24 INFORMATION FOR SEQ ID NO:158: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1..23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:158: ATGAATTCCA TCTTTTATTC CAC 23 INFORMATION FOR SEQ ID NO:159: SEQUENCE CHARACTERISTICS: LENGTH: 27 base pairs TYPE: nucleic acid WO 98/18323 PCT/US97/19575 -233- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...27 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159: AACCATGGTG ATTTTAAGCA TTGAAAG 27 INFORMATION FOR SEQ ID NO:160: SEQUENCE CHARACTERISTICS: LENGTH: 28 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...28 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:160: AAGAATTCCA CTCAAAATTT TTTAACAG 28 INFORMATION FOR SEQ ID NO:161: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCT/US97/19575 -234- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:161: GATCATCCAT ATGTTATCTT CTAAT INFORMATION FOR SEQ ID NO:162: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162: TGAATTCAAC CATTTTAACC CTG 23 INFORMATION FOR SEQ ID NO:163: SEQUENCE CHARACTERISTICS: LENGTH: 27 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: I I WO 98/18323 PCT/US97/19575 -235- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...27 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:163: TATACCATGG TGAAATTTTT TCTTTTA 27 INFORMATION FOR SEQ ID NO:164: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:164: AGAATTCAAT TGCGTCTTGT AAAAG INFORMATION FOR SEQ ID NO:165: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...24 WO 98/18323 PCT/US97/19575 -236- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:165: TATACCATGG TGATGGACAA ACTC 24 INFORMATION FOR SEQ ID NO:166: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:166: ATGAATTCCC ACTTGGGGCG ATA 23 INFORMATION FOR SEQ ID NO:167: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:167: TTATGGATCC AAACCAATTA AAACT v WO 98/18323 PCT/US97/19575 -237- INFORMATION FOR SEQ ID NO:168: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:168: TATCTCGAGT TATAGAGAAG GGC 23 INFORMATION FOR SEQ ID NO:169: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1....22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:170: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid WO.98/18323 PCT/US97/19575 -238- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: (A).NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:170: TAGAATTCGC CTCTAAAACT TTAG 24 INFORMATION FOR SEQ ID NO:171: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:171: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:172: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic)

,J

WO 98/18323 PCT/US97/19575 -239- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172: TAGAATTCGC ATAACGATCA ATC 23 INFORMATION FOR SEQ ID NO:173: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:173: ATATCCATGG TGAGTTTGAT GA 22 INFORMATION FOR SEQ ID NO:174: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: r' WO 98/18323 PCT/US97/19575 -240- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:174: ATGAATTCAA TTTTTTATTT TGCCA INFORMATION FOR SEQ ID NO:175: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:175: AATTCCATGG CTATCCAAAT CCG 23 INFORMATION FOR SEQ ID NO:176: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...25 WO 98/18323 PCT/US97/19575 -241 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:176: ATGAATTCGC CAAAATCGTA GTATT INFORMATION FOR SEQ ID NO:177: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:177: GATACCATGG AATTTATGAA AAAG 24 INFORMATION FOR SEQ ID NO:178: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:.

ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:178: TGAATTCGAA AAAGTGTAGT TATAC WO 98/18323 PCT/US97/19575 -242 INFORMATION FOR SEQ ID NO:179: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:179: CCCTTCATTT TAGAAATCG 19 INFORMATION FOR SEQ ID NO:180: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:180: ATTTCAACCA ATTCAATGCG INFORMATION FOR SEQ ID NO:181: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid WO 98/18323 PCT/US97/19575 -243- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:181: GCCCCTTTTG ATTTGAAGCT INFORMATION FOR SEQ ID NO:182: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:182: TCGCTCCAAG ATACCAAGAA GT 22 INFORMATION FOR SEQ ID NO:183: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCT/US97/19575 -244 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:183: CTTGAATTAG GGGCAAAGAT CG 22 INFORMATION FOR SEQ ID NO:184: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:184: ATGCGTTTTT ACCCAAAGAA GT 22 INFORMATION FOR SEQ ID NO:185: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: I WO 98/18323 PCT/US97/19575 -245 ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:185: ATAACGCCAC TTCCTTATTG GT 22 INFORMATION FOR SEQ ID NO:186: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:186: CTTTGGGTAA AAACGCATC 19 INFORMATION FOR SEQ ID NO:187: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...20

I~

WO 98/18323 PCT/US97/19575 -246- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:187: CGATCTTTGA TCCTAATTCA INFORMATION FOR SEQ ID NO:188: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:188: ATCAAGTTGC CTATGCTGA 19 INFORMATION FOR SEQ ID NO:189: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:189: TTGAACACTT TTGATTATGC GG 22 WO 98/18323 PCTIUS97/19575 -247- INFORMATION FOR SEQ ID NO:190: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:190: GGATTATGCG ATTGTTTTAC AAG 23 INFORMATION FOR SEQ ID NO:191: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:191: GTCTTTAGCA AAAATGGCGT C 21 INFORMATION FOR SEQ ID NO:192: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid

I'

WO 98/18323 PCT/US97/19575 -248- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:192: AATGAGCGTA AGAGAGCCTT C 21 INFORMATION FOR SEQ ID NO:193: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:193: CTTATGGGGG TATTGTCA 18 INFORMATION FOR SEQ ID NO:194: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCTIUS97/19575 -249- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:194: AGCATGTGGG TATCCAGC 18 INFORMATION FOR SEQ ID NO:195: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:195: AGGTTGTTGC CTAAAGACT 19 INFORMATION FOR SEQ ID NO:196: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/18323 PCT/US97/19575 -250- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:196: CTGCCTCCAC CTTTGATC 18 INFORMATION FOR SEQ ID NO:197: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:197: ACCAATATCA ATTGGCACT 19 INFORMATION FOR SEQ ID NO:198: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 WO 98/18323 PCT/US97/19575 -251- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:198: ACTTGGAAAA GCTCTGCA 18 INFORMATION FOR SEQ ID NO:199: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:199: CTTGCTTGTC ATATCTAGC 19 INFORMATION FOR SEQ ID NO:200: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:200: GTTGAAGTGT TGGTGCTA i WO.98/18323 PCT/US97/19575 -252- INFORMATION FOR SEQ ID NO:201: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:201: CAAGCAAGTG GTTTGGTTTT AG 22 INFORMATION FOR SEQ ID NO:202: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:202: TGGAAAGAGC AAATCATTGA AG 22 INFORMATION FOR SEQ ID NO:203: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid WO 98/18323 PCT/US97/19575 -253 STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:203: GCCCATAATC AAAAAGCCCA T 21 INFORMATION FOR SEQ ID NO:204: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:204: CTAAAACCAA ACCACTTGCT TGTC 24 INFORMATION FOR SEQ ID NO:205: SEQUENCE CHARACTERISTICS: LENGTH: 16 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/18323 PCT/US97/19575 -254- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...16 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:205: GTAAAACGAC GGCCAG 16 INFORMATION FOR SEQ ID NO:206: SEQUENCE CHARACTERISTICS: LENGTH: 17 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...17 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:206: CAGGAAACAG CTATGAC 17 INFORMATION FOR SEQ ID NO:207: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO. 98/18323 PCT/US97/19575 -255- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:207: ATCTTACCTA TCACCTCAAA T 21 INFORMATION FOR SEQ ID NO:208: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:208: AGACAGCAAC ATCTTTGTGA A

Claims

1. An isolated nucleic acid comprising a nucleotide sequence encoding an H pylori polypeptide comprising an amino acid sequence that has at least about homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, SEQIDNO: 80, SEQIDNO: 81 and SEQ ID NO: 112.

2. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori polypeptide comprising an amino acid sequence that has at least about homology with an amino acid sequence selected from the group consisting of SEQ ID NO:

74-SEQ ID NO: 146. ~5 3. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 74-SEQ ID NO: 146. 4. An isolated nucleic acid which encodes an H. pylori polypeptide, the nucleic 20 acid comprising a nucleotide sequence that has at least about 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 37, SEQ IDNO: 39, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 55 and SEQ ID NO: 61, or a complement thereof. 25 5. An isolated nucleic acid which encodes an H. pylori polypeptide, the nucleic acid comprising a nucleotide sequence that has at least about 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 73, or a complement thereof. 6. The isolated nucleic acid of claim 2, comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 73, or a complement thereof. 7. An isolated nucleic acid molecule encoding an H. pylori polypeptide, the nucleic acid comprising a nucleotide sequence which hybridizes under stringent Oxybridization conditions to a nucleic acid molecule comprising the nucleotide sequence cted from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, i "7 O 257 SEQ ID NO: 11, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: SEQ ID NO: 55 and SEQ ID NO: 61, or a complement thereof. 8. An isolated nucleic acid molecule encoding an H. pylori polypeptide, the nucleic acid comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 73, or a complement thereof. 9. An isolated nucleic acid comprising a nucleotide sequence of at least 8 nucleotides in length, wherein the sequence hybridizes under stringent hybridization conditions to a nucleic acid having a nucleotide sequence selected from the group consisting of SEQ ID NO: I-SEQ ID NO: 73, or a complement thereof. 10. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cell envelope polypeptide or a fragment thereof, said nucleic acid comprising a nucleotide sequence that has at least 60% homology with a nucleotide sequence selected S from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, SEQ ID NO: 48, SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 20 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, SEQ ID NO: 71, SEQ ID NO: 17, SEQ ID NO: 57, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, and SEQ ID NO: 21, or a complement thereof. 1. The isolated nucleic acid of claim 10, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that has at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, and SEQ ID NO: 48, or a complement thereof. 12. The isolated nucleic acid of claim 10, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that has at s least 60% homology with a nucleotide sequence selected from the group consisting of SEQ p' 1- NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID S258 NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71, or a complement thereof. 13. The isolated nucleic acid of claim 12, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that has at least 60% homology with a o1 nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 1 1 and SEQ ID NO:71, or a complement thereof. 14. The isolated nucleic acid of claim 12, wherein said H. pylori outer membrane is polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that has at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: .:20 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, or a complement thereof. 15. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cell envelope polypeptide or a fragment thereof comprising an amino acid sequence ::25 that has at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 130, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, and SEQ ID NO: 94. 16. The isolated nucleic acid of claim 15, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a qgment thereof comprising an amino acid sequence that has at least 60% homology with 259 an amino acid sequence selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, and SEQ ID NO: 121. 17. The isolated nucleic acid of claim 15, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof comprising an amino acid sequence that has at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID to NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, and SEQ ID NO: 130. 18. The isolated nucleic acid of claim 17, wherein said H. pylori outer membrane 15 polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof and comprising an amino acid sequence that has at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, and SEQ ID NO: 84 and SEQ ID NO: 144. 19. The isolated nucleic acid of claim 17, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence that has at least 60% homology with an amino acid sequence selected from the group consisting of 25 SEQ ID NO: 89, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, and SEQ ID NO:

131. 20. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori secreted polypeptide or a fragment thereof, said nucleic acid comprising a nucleotide sequence that has at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 72, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ I) NO: 36, SEQ ID NO: 38, SEQ ID NO: ST SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 53. 260 SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, and SEQ ID NO: 68, or a complement thereof. 21. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori secreted polypeptide or a fragment thereof comprising an amino acid sequence that has at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 95, SEQ ID NO: 102, SEQ ID NO: 104, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, and SEQ ID NO: 141. 22. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cellular polypeptide or a fragment thereof, said nucleic acid comprising a nucleotide sequence that has at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 73, or a *20 complement thereof. 23. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cellular polypeptide or a fragment thereof comprising an amino acid sequence that has at least 60% homology with an amino acid sequence selected from the group consisting .25 of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ED NO: 142, SEQ ID NO: 143, and SEQ ID NO: 146. 24. The isolated nucleic acid of any one of claims 1 to 5 and 10 to 23, wherein said level of homology is at least The isolated nucleic acid of any one of claims 1 to 5 and 10 to 23, wherein said level of homology is at least 3-5s 26. The isolated nucleic acid of any one of the claims I to 5 and 10 to 23, wherein 4 <'S;aid level of homology is at least 261 27. The isolated nucleic acid of any one of claims 1 to 5 andl0 to 23, wherein said level of homology is at least 28. The isolated nucleic acid of any one of claims 1 to 5 and 10 to 23, wherein said level of homology is at least 98%. 29. The isolated nucleic acid of any one of claims 1. to 5 and 10 to 23, wherein said level of homology is at least 99%. The isolated nucleic acid of any one of claims 1 to 5 and 10 to 23, wherein said level of homology is 100%. 31. A probe comprising a nucleotide sequence consisting of at least 8 consecutive nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1- SEQ ID NO: 73, or a complement thereof. 32. A recombinant expression vector comprising the nucleic acid of any one of claims 1 to 30 operably linked to a transcription regulatory element. S 33. A cell comprising a recombinant expression vector of claim 32. 34. A method for producing an H. pylori polypeptide comprising culturing a cell of claim 33 under conditions that permit expression of the polypeptide. The method of claim 34, further comprising purifying the polypeptide from the cell. 36. A method for detecting the presence of a Helicobacter nucleic acid in a sample comprising: contacting a sample with a nucleic acid of any of claims 1 to 30 so that a hybrid can form between the probe and a Helicobacter nucleic acid in the sample; and detecting the hybrid formed in step wherein detection of a hybrid indicates the presence of a Helicobacter nucleic acid in the sample. 37. An isolated H. pylori polypeptide comprising an amino acid sequence having at least about 60% homology with an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 80, SEQ ID NO: 81 and SEQ ID NO: 112. 38. An isolated H. pylori polypeptide comprising an amino acid sequence having at least about 60% homology with an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 74-SEQ ID NO: 146. 39. An isolated H. pylori polypeptide which is encoded by a nucleic acid to comprising a nucleotide sequence having at least about 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 55 and SEQ ID NO: 61. 40. An isolated H. pylori polypeptide which is encoded by a nucleic acid comprising a nucleotide sequence having at least about 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 73. 41. The isolated H. pylori polypeptide of claim 40, wherein said polypeptide is 20 encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: I- SEQ ID NO: 73. 42. An isolated H. pylori polypeptide which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid selected from the 25 group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 11, o*o SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: and SEQ ID NO: 61, or a complement thereof. o* 43. An isolated H. pylori polypeptide which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 73, or a complement thereof. 44. An isolated H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 74-SEQ ID NO: 146. 263 An isolated H. pylori cell envelope polypeptide or a fragment thereof, wherein said polypeptide comprises an amino acid sequence having at least 60% homology with an amino acid sequence that is selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID.NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 130, SEQ ID NO: 78, SEQ 1D NO: 79, SEQ ID NO: 81, and SEQ ID NO: 94. 46. The isolated polypeptide of claim 45, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a fragment thereof comprising an amino acid sequence having at least 60% homology with an amino acid sequence that selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, and SEQ ID NO: 121. 47. The isolated polypeptide of claim 45, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof comprising an amino acid sequence having at least 60% homology with 20 an amino acid sequence selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID S NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID 25 NO: 144, SEQ ID NO: 90, and SEQ ID NO: 130. 48. The isolated polypeptide of claim 47, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof comprising an amino acid sequence having at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, and SEQ ID NO: 84 and SEQ ID NO: 144. 49. The isolated polypeptide of claim 47, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence having at 264 least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, and SEQ ID NO: s 131. An isolated H. pylori cell envelope polypeptide or a fragment thereof, wherein said polypeptide is encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: io SEQ ID NO: 48, SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18. SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1. SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, SEQ ID NO: 71, SEQ ID NO: 17, SEQ ID NO: 57, SEQ ID NO: 5, SEQ Is ID NO: 6, SEQ ID NO: 8, and SEQ ID NO: 21. 51. The isolated polypeptide of claim 50, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori inner membrane polypeptide or a fragment thereof encoded by a nucleotide sequence having at least 60% homology with a 20 nucleotide sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: and SEQ ID NO: 48. 52. The isolated polypeptide of claim 50, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a 25 fragment thereof encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71. 53. The isolated polypeptide of claim 52, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected 265 from the group consisting of SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11 and SEQ ID NO:71. 54. The isolated polypeptide of claim 52, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 0o 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58. An isolated H. pylori cellular polypeptide or a fragment thereof, wherein said polypeptide comprises an amino acid sequence having at least 60% homology with an amino acid sequence that is selected from the group consisting of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 142, SEQ ID NO: 143, and SEQ ID NO: 146. a 56. An isolated H. pylori cellular polypeptide or a fragment thereof, wherein said 20 polypeptide is encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: SEQID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 73. 57. An isolated H. pylori secreted polypeptide or a fragment thereof, wherein said polypeptide comprises an amino acid sequence having at least 60% homology with an amino acid sequence that is selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 95, SEQ ID NO: 102, SEQ ID NO: 104, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 122, SEQ ID NO: 126, SEQ D NO: 132, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, and SEQ ID NO: 141. S266 58. An isolated H. pylori secreted polypeptide or a fragment thereof, wherein said polypeptide is encoded by a nucleotide sequence having at least 60% homology with a nucleotide sequence selected from the group consisting of SEQ ID NO: 72, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 53, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, and SEQ ID NO: 68. 59. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein said level of homology is at least The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein said level of homology is at least 61. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein said level of homology is at least 62. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein 20 said level of homology is at least 63. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein said level of homology is at least 98%. 5 64. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein S said level of homology is at least 99%. 65. The isolated polypeptide of any one of claims 37 to 40 and 45 to 58, wherein said level of homology is 100%. 66. A fusion protein comprising an H. pylori polypeptide which comprises an amino acid sequence having at least 60% homology with an amino acid sequence selected from the group consisting of SEQ ID NO: 74-SEQ ID NO: 146 operatively linked to a non- H. pylori polypeptide. 267 67. A vaccine formulation for prophylaxis or treatment of an H. pylori infection comprising an effective amount of at least one isolated nucleic acid of any of claims I to s 68. A vaccine'formulation for prophylaxis or treatment of an H. pylori infection comprising an effective amount of at least one H. pylori polypeptide or a fragment thereof of any of claims 37 to 69. A vaccine formulation of claim 67 or 68, further comprising a pharmaceutically acceptable carrier. A vaccine formulation of claim 69, wherein the pharmaceutically acceptable carrier comprises an adjuvant. 15 71. A vaccine formulation of claim 69, wherein the pharmaceutically acceptable carrier comprises a delivery system. S" 72. The vaccine composition of claim 68, including a substance selected from cholera toxin, a non-toxic derivative of cholera toxin, procholeragenoid, a fungal 20 polysaccharide, muramyl dipeptide, a muramyl dipeptide derivative, a phorbol ester, E. coli labile toxin, a non-H. pylori bacterial lysate, a block polymer, a saponin, biodegradable microaspsules, ISCOMs, cochleates, liposomes, a genetically engineered attenuated live virus or bacteria, and a recombinant virus-like particle. 25 73. The vaccine composition of claim 67, including a genetically engineered attenuated live virus or bacteria, or a recombinant virus-like particle. 74. Use of the nucleic acid of any one of claims 1 to 30, in the manufacture of a vaccine composition, for treating a subject for Helicobacter pylori infection. The use according to claim 74, wherein the treatment is a prophylactic treatment. 76. The use according to claim 74, wherein the treatment is a therapeutic treatment. 268 77. Use of a purified polypeptide according to any one of claims 37 to 65, in the manufacture of a vaccine composition, for treating a subject for Helicobacter pylori infection. 78. The use according to claim 77, wherein the treatment is a prophylactic treatment. 79. The use according to claim 77, wherein the treatment is a therapeutic treatment. 80. A drug screening assay comprising the step of contacting a test compound with a purified polypeptide comprising an amino acid sequence that has at least 60% homology with an amino acid sequence shown in the sequence listing. 81. The assay of claim 80, comprising, determining if the compound binds to said Is amino acid sequence of the purified polypeptide. 82. The assay of claim 80 or 81, comprising determining if the test compound S alters the binding affinity of said amino acid sequence of the purified polypeptide for a ligand thereof. 83. The assay of claim 82, wherein the ability of the test compound to inhibit the binding ability of said amino acid sequence to the ligand is determined. 84. The assay of claim 80 or 81, wherein the polypeptide has enzymatic activity, 25 and the assay comprises detecting if the test compound changes the enzymatic activity. 85. The assay of claim 84, wherein the enzymatic activity produces a detectable reaction product with distinctive absorption, fluorescence or chemi-luminescence properties. 86. The assay of any one of claims 80 to 85, wherein the assay is a cell-free assay. S7. The assay of any one of claims 80 to 86, wherein the amino acid sequence comprised by the puified polypeptide is at least 70%. 80%, 90%, 95%, 9 or 99% hornologous to an amino acid sequence shown in the sequence listing. or identical to an YS <Tk tmino acid sequence shown in the sequence listing. 269 88. A drag screening assay comprising the step of contacting a test compound with an isolated nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence shown in the sequence listing. 89. The assay of claim 88, comprising determining if the compound binds to, or interacts with, said nucieotide sequence of the nucleic acid. The assay of claim 88, wherein the assay is an in vitro assay. 91. The assay of any one of claims 88 to 90, wherein the nucleotide sequence comprised by the nucleic acid is at least 70%, 80%, 95%, 98%, or 99% homologous to a nucleotide sequence shown in the sequence listing, or identical to a nucleotide sequence shown in the sequence listing. DATED this 31 day of December 1999 By its Patent Attorneys, E. F. WELLNGTON CO. By: .e gig• *oooo o*