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WO1996000238A1 - Epitopes de lymphocytes t d'allergene du pollen de ray-grass - Google Patents

Epitopes de lymphocytes t d'allergene du pollen de ray-grass Download PDF

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Publication number
WO1996000238A1
WO1996000238A1 PCT/GB1995/001493 GB9501493W WO9600238A1 WO 1996000238 A1 WO1996000238 A1 WO 1996000238A1 GB 9501493 W GB9501493 W GB 9501493W WO 9600238 A1 WO9600238 A1 WO 9600238A1
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WO
WIPO (PCT)
Prior art keywords
amino acid
polypeptide
sequence
acid residue
rye grass
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB1995/001493
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English (en)
Inventor
Ian Victor Lewin
Ali Gholam Bungy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Pasteur Holding Ltd
Original Assignee
Peptide Therapeutics Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Peptide Therapeutics Ltd filed Critical Peptide Therapeutics Ltd
Priority to EP95922664A priority Critical patent/EP0772629A1/fr
Priority to JP8502928A priority patent/JPH10506877A/ja
Priority to AU27487/95A priority patent/AU707740B2/en
Publication of WO1996000238A1 publication Critical patent/WO1996000238A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • the present invention relates to the immunodominant T cell epitope of rye grass, its minimal sequence, its role in hayfever and its use in the manufacture of a medicament for the treatment or prophylaxis of hayfever.
  • Amino acid residue symbols used hereafter are those identified by the IUPAC-ID3 Biochemical Nomenclature Commission and they include all D or amino acids or analogues and derivatives thereof.
  • the symbol X represents an unidentified amino acid or analogue thereof.
  • Lol pi The major fraction cf Lolium perenne ( . perenne) has been found to be Lol pi, a gl coprotein of 240 amino acid residues, and most hayfever sufferers in Europe sensitive to grass pollen (about 80%) possess specific IgE antibodies to this protein.
  • the complete sec-.iei-.ce of Lol pi has been published and it has been suggested that there is a polypeptide sequence of 14 consecutive amino acid residues which includes the immunogenic determinant of Lol pi. (Bungy et al . Clin Exp Immunol 1993, 94. 111-116) .
  • Immunotherapy using native allergen to reduce the sensitivity of patients has the disadvantage that all sensitising agents have the potential to induce severe allergic reactions such as bronchospasm, anaphylaxis and even death.
  • Hayfever symptoms are brought about through specific lymphocyte activation leading to the release of vasoactive amine mediators (e.g. histamine) from cells into extracellular space.
  • vasoactive amine mediators e.g. histamine
  • the role of IgE antibodies in mediating allergic reactions is well known.
  • the ability to trigger T cells could be used in the production of antibodies to a B cell epitope by combination of this B cell epitope with a T cell epitope.
  • Such antibodies could be used to block the IgE mediated response to allergen (for example blocking of binding of IgE to cells) .
  • IgE comprises two light polypeptide chains and two heavy polypeptide chains linked by disulphide bonds.
  • the heavy chains have one variable domain (V H ) and four constant domains (C H 1, C H 2, C H 3 and C frustration4 also known as C ⁇ l, C JJ 2, C E 3 and C E 4) .
  • a region of IgE which comprises part of the heavy chains is known as the Fc region.
  • WO 90/15878 describes certain immunoactive peptides and antibodies and their use in allergy treatment by prevention of the triggering of the release of histamine.
  • the Stanworth application described an immunogen comprising a residue of a histamine-releasing peptide comprising a cationic N-terminal head and a hydrophobic C-terminal tail, together with a residue capable of eliciting antibodies against said peptide whilst inhibiting histamine-release by said peptide is useful in anti- allergy treatment.
  • the histamine-releasing peptide is of formula: KTKGSGFFVF [SEQ ID:2] , optionally amidated at the C-terminal.
  • Antibodies to the histamine-releasing peptide are used for passive immunisation.
  • the minimal T cell epitope of rye grass which is an immunodominant 9-mer polypeptide active in stimulating T cells from atopic patients with hayfever.
  • T cells specifically sensitive to any or some of the individual proteins Lol pi, Lol pll and Lol pill may be stimulated by this immunodominant 9-mer.
  • polypeptide having nine amino acid residues and including the six amino acid sequence VXRIDT [SEQ ID:3] .
  • the sequence VXRIDT may be referred to as the T cell epitope motif.
  • polypeptide having a sequence of nine amino acid residues of the sequence AVWRIDTPD [SEQ ID:5] or VWRIDTPDK [SEQ ID:6] which has 0, 1 or 2 of its amino acid residues substituted for any other amino acid residue.
  • polypeptides of the present invention having nine amino acid residues may be complexed to a hapten (e.g. phosphorylcholine or 2,4 dinitrophenyl) or a pharmacologically acceptable carrier or both; complexed either directly or linked indirectly by way of a spacer such as a polypeptide or a hydrocarbon or co- administered.
  • a conjugate comprising a pharmacologically acceptable carrier and a polypeptide having nine amino acid residues including the T cell epitope motif VXRIDT, or nine amino acid residues of the sequence XVXRIDTXX, or the sequence AVWRIDTPD or VWRIDTPDK having 0, 1 or 2 of its amino acid residues substituted for any other amino acid residue.
  • a ligand comprising an antibody domain specific for the nine amino acid polypeptide of the present invention. This antibody domain may be mono- or polyclonal or antigen binding fragments thereof.
  • the immunodominant 9-mer polypeptide of the invention may be used to induce T cell activation. This, in turn, could lead to T cell anergy, diminution or lack of responsiveness to an antigen.
  • the present invention provides an immunogen comprising a residue of a histamine releasing peptide comprising a cationic N-terminal head and a hydrophobic C-terminal tail, together with a residue capable of eliciting antibodies against this peptide, together with a 9-mer polypeptide as previously described.
  • a purpose of this second aspect of the present invention is to induce production of antibodies to the immunogen in individuals sensitive to rye grass pollen.
  • the present invention can include an immunogen comprising a residue of a histamine-releasing peptide which has a cationic N-terminal head comprising the sequence KTK, and a hydrophobic C-terminal tail comprising the sequence FF.
  • the C-terminal may be blocked by amidation.
  • the N-terminal head may be separated from the C-terminal tail by from two to six predominantly non- polar and non-hydrophobic amino acid residues (for example GSG) .
  • the present invention can provide an immunogen including the peptide sequence KTKGSGFFVF, together with a polypeptide having 9 amino acid residues as described above, wherein the 9-mer polypeptide is complexed directly to the immunogen or is indirectly linked e.g. by way of a spacer such as a polypeptide or hydrocarbon or the 9-mer polypeptide is co-administered with the immunogen.
  • the present invention provides an immunogen which includes both a residue of a histamine-releasing polypeptide having the sequence KTKGSGFFVF, and a T cell epitope polypeptide having the sequence AVWRIDTPD, either complexed directly or linked indirectly e.g. by way of a spacer such as a polypeptide or hydrocarbon or the 9-mer polypeptide is co-administered with the immunogen.
  • a spacer such as a polypeptide or hydrocarbon or the 9-mer polypeptide is co-administered with the immunogen.
  • the C-terminal of the immunogen is blocked by amidation.
  • the present invention provides a method of using the above compounds and immunogens of the present invention in the manufacture of a medicament for the treatment or prophylaxis of allergies particularly of rye grass allergy or hayfever.
  • the present invention provides a method for treatment or prophylaxis of allergies particularly of rye grass allergy or hayfever, by administration of an effective amount of the above compounds or immunogens.
  • Medicaments made according to the invention may be administered to patients by any of the administration methods already known to those skilled in the art.
  • the present invention provides an assay for sensitivity to rye grass allergens and hence to determination of hayfever sufferance.
  • peripheral blood mononuclear cells PBMCs
  • PBMCs peripheral blood mononuclear cells
  • lymphocyte activation may be measured using thymidine incorporation as determinant.
  • Cells from subjects allergic to any of the main allergens of rye grass would be expected to react.
  • the present invention provides an assay for specific T cell populations sensitive to rye grass allergen, such as Lol pi, by testing for reaction to the 9-mer described above, selecting reactive T cells and forming therefrom T cell lines, and cloning therefrom a T cell clone having specificity for the 9-mer.
  • rye grass allergen such as Lol pi
  • Figure 1 shows the peripheral blood mononuclear cell response of an atopic patient (code name AS3) to Lol pi;
  • Figure 2 shows PBMC responses to 20 peptide pools
  • FIG. 3 shows the decoding of the immunodominant Pool 17
  • Figure 4 shows dose response curves for peptides of Pool 17
  • Figure 5 shows PBMC responses of atopic patient AS3 to 9 mer peptides
  • FIG. 6 shows T cell line specificity for Lol pi
  • Figure 7 shows a comparison of T cell line and PBMC responses to 9-mer peptides
  • Figure 8 shows the results of Lysine substitution when each amino acid residue of the 14 amino acid polypeptide thought to include the T cell epitope of Lol pi was individually substituted for Lysine;
  • Figure 9 shows the results of Glycine substitution when each amino acid residue of the 14 amino acid residue polypeptide thought to include the T cell epitope of Lol pi was individually substituted for Glycine.
  • Rye grass (Loliu perenne) pollen extract was supplied by Dome Laboratories (Stoke Court, U.K.) and subjected to 33% ammonium sulphate precipitation.
  • the -supernatant was dialysed against phosphate buffer saline (PBS) .
  • the dialysed sample was injected on to FPLC (fast protein liquid chromatography) (Pharmacia, LKB, Sweden) for protein separation on a gel filtration column Superose 12, and 0.3 ml fractions were collected.
  • FPLC fast protein liquid chromatography
  • SDS polyacrylamide-gel electrophoresis
  • the apparent molecular mass of the allergens was estimated by using prestained protein standards.
  • the iso-allergen clone 5A of Lol pi consists of 240 amino acids.
  • a set of 115 overlapping, 12-mer peptides spanning the entire length of the iso-allergen clone 5A of the Lol pi was synthesized on polyethylene rods (pins) using the multi-pin technique which enables the rapid mapping of T cell determinants. All of the peptides were acetylated at the N terminus and, as a result of cleavage from the pins, had a C- terminal diketopiperazine (DKP) group.
  • DKP diketopiperazine
  • a ⁇ -alanine residue was incorporated to space the defined sequence from the DKP group.
  • the peptides were released from the solid phase according to the method of Maeji et al. using 0.1M phosphate buffer (pH 7) for 4 hours at room temperature. Sets of six continuous peptides were pooled, with the exception of Pools-1 and 15 (5 peptides) and Pool-20 (3 peptides) . Therefore, 20 peptide pools were used for epitope mapping. The purity of selected peptides including all peptides in Pool-17, was established by reverse phase HPLC analysis and the amino acid composition was checked by amino acid analysis.
  • Heparinized venous blood was diluted 1:1 with RPMI 1640 and layered onto Lymphoprep (Nycomed, Oslo, Norway) . The gradients were centrifuged at 400g for 25 minutes at room temperature.
  • Mononuclear cells were harvested and washed twice in RPMI 1640 (Gibco, Grand Island, NY, USA) and then resuspended at a concentration of 2x10 s cells/ml in RPMI supplemented with 10% human AB-serum (ICN Flow, Bucks, U.K.), 2mM 1-glutamine and 20 ⁇ g/ml gentamicin (Gibco, Grand Island, NY, USA) . Cells were cultured at a concentration of 2 x 10 5 per well in 0.2 ml of complete medium in U-bottomed 96-well microtiter plates.
  • PBMC peripheral blood mononuclear cells proliferative responses to the major purified fraction of L. perenne (Lol pi) were found (Fig.l) .
  • This dose ranging experiment shows the typical bell-shaped dose response curve of lymphocyte activation seen with allergen and antigen.
  • the peak incorporation of tritiated thymidine is seen at lO ⁇ g/ml of purified Lol pi. This is evidence of lymphocyte reactivity to the major fraction of Rye grass protein in atopic subjects.
  • Atopies responded to both Lol pi and LPE as might be expected. Non-atopies did not respond to Lol pi but some did show minor stimulation with LPE.
  • T cell epitopes in the 20 pools of peptides was investigated by in vitro proliferation tests on PBMC of six rye grass-sensitive patients and seven non-atopic control subjects. Whilst five out of the six patients responded to Pool 17, patient B reacted to Pool 15 and 19. In addition, patient E responded to Pool 6 and patient F also responded to Pool 13. Pool 17 clearly contained the immunodominant epitope. Non- atopic subjects did not respond to any of the 20 peptide pools. There was no class II MHC (major histocompatibility complex) Dr restriction in the atopic subjects.
  • Fig. 2 The number of wells containing peripheral blood mononuclear cells giving positive proliferative responses to 20 different peptide pools spanning the entire length of the Lol pi is shown in Fig. 2.
  • Each pool was composed of 6 (except 1, 15 and 20) overlapping 12-mer peptides offset by 2 residues, and thus spanned 22 residues of the protein sequence, and was tested against 12 identical cultures from each patient.
  • These data identify Pool 17 as containing the major epitope of rye grass.
  • the cut-off for significance in terms of number of wells responding is defined by statistical methods based on the Poisson distribution.
  • Pool 17 is statistically different from all other pools tested.
  • Further data from other atopic subjects confirmed the immunodominance of Pool 17.
  • Pool 17 is statistically different from all the other pools tested.
  • Further data from other atopic subjects confirmed the immunodominance of Pool 17.
  • Pool 17 consists of 6 overlapping peptides covering a span of 22 amino acids.
  • peptides 3 and 4 of Pool 17 were the main stimulatory peptides in vitro (Fig. 3) .
  • the active polypeptides of Lol pi (3) are 139 WGAVWRIDTPDK 204 [SEQ ID:9] and (4) 19S AVWRIDTPDKLT 206 [SEQ ID:10] and are each as active in lymphoproliferative assays as is the whole pool.
  • PBMCs were incubated with a range of concentration of a) Pool 17, b) peptide 4 of Pool 17 and c) Pool 8 (a non-stimulatory peptide pool) .
  • Cells were harvested after 6 days in culture.
  • Figure 5 shows the percentage of wells containing peripheral blood mononuclear cells from a rye grass sensitive patient (AS3) giving positive proliferative responses to single peptides of the 9-mer peptides spanning the entire length of the immunodominant epitope of the Lol pi.
  • the 9 amino acid residue polypeptide of sequence (5) AVWRIDTPD is found to be the most active of any 9, 10, 11, 12, 13 or 14 amino acid residue polypeptide spanning the length of the two continuous immunodominant polypeptides.
  • the 9 amino acid residue polypeptide of sequence (6) VWRIDTPDK was also found to be active. More surprisingly, six amino acid residues were found to be the most important in determining whether the polypeptide is immunodominant.
  • T cell line responses to 9-mer peptides were investigated.
  • Lol pi-specific T cell lines were obtain as follows: 0.5 x 10 6 PBMCs per ml from patient AS3 who reactive to the immunodominant T cell epitope were stimulated with Lol pi (lO ⁇ g/ml) in PRMI 1640 supplemented with 2mM L-glutamine, 5 x 10" 5 M 2- mercaptoethanol, 20 ⁇ g/ml gentamicin, and 10% human AB serum in 24-well flat-bottomed culture plates for 5 days. Subsequently, human recombinant IL-2 (hrIL-2) (25 units/ml) was added and kept in culture for an additional 7 days.
  • hrIL-2 human recombinant IL-2
  • T cell blasts were then separated by a Ficoll-Hypaque density gradient and Lol pi specificity of T cell line was assessed.
  • the specificity of the T cell lines produced by stimulation with IL-2 and Lol pi was checked.
  • 5 x 10 4 T cell line cells were incubated in duplicate 200 ⁇ l cultures in the presence of 5 x 10" irradiated autologous antigen presenting cells (APCs) plus 1, 5 and 10 ⁇ g/ml of Lol pi in 96-well round-bottomed microtiter plates for 3 days at 37°C, in a humidified atmosphere of 5% C0 2 , then pulsed overnight with 0.4 ⁇ Ci/well 3H-thymidine.
  • APCs autologous antigen presenting cells
  • Radionuclide uptake was measured by scintillation counting. As shown in Fig. 6, using a dose response of Lol pi from 1 ⁇ g/ml to 10 ⁇ g/ml it is clear that this T cell line is specific for Lol pi. T cell line (T) plus irradiated APC* (A) gives low background counts in comparison.
  • 5 x 10 4 T cell line cells were incubated in duplicate 200 ⁇ l cultures in the presence of 5 x 10 4 irradiated autologous APCs plus 7.5 ⁇ g/well of individual single peptide of the 9-mers in 96-well round-bottomed microtiter plates for 3 days at 37°C, in a humidified atmosphere of 5% C0 2 , then pulsed overnight with 0.4 ⁇ Ci/well 3H-thymidine. Radionuclide uptake was measured by scintillation counting. Two peptides (5) and (6) are clearly more active in stimulating T cell lines from an atopic donor than other peptides.
  • FIG. 7 A comparison of PBMC and T cell line responses (Fig. 7) shows that the T cell line and PBMC respond similarly.
  • the nine amino acid residue polypeptide including the T cell epitope motif VXRIDT, or nine amino acid residues having the sequence XVXRIDTXX, or the sequence AVWRIDTPD or VWRIDTPDK wherein 0, 1 or 2 of the amino acid residues is substituted for any other amino acid residue is the common immunodominant T cell epitope of rye grass.
  • the existence of a common epitope motif in rye grass was not obvious and its identification is of considerable clinical significance. In other areas of plant allergy (e.g. ragweed allergy) it has not been possible so far to characterise a common epitope to all of the various major allergy inducing proteins.
  • the surprising characterisation of a T cell epitope motif and an immunodominant T cell epitope for rye grass for the first time allows the possibility of a previously impossible detailed analysis of the molecular environment of the immune response to rye grass allergen.
  • the motif and epitope can be modelled to determine the shape and configuration of the polypeptides, the spatial distribution of charges, the level of steric constraint on the molecules etc. so as to determine the relationship between structure and activity.
  • those skilled in the art could form analogs or mimetics of the motif and epitope, which would exhibit essentially the same or similar functional activity whilst differing in chemical formula. For example some or all amino acid residues could be replaced by equivalent non-amino- acid moieties. It is intended that the present invention should cover such functionally active analogue or mimetic T cell epitope or motif equivalents.
  • Val Xaa Arg lie Asp Thr
  • Val Trp Arg lie Asp Thr Pro Asp Lys
  • Trp Gly Ala Val Trp Arg lie Asp Thr Pro Asp Lys 1 5 10
  • Trp Arg lie Asp Thr Pro Asp Lys Leu Thr Gly Pro 1 5 10
  • Trp Gly Ala Val Trp Arg lie Asp Thr
  • Trp Arg lie Asp Thr Pro Asp Lys Leu 1 5
  • Trp Asp Ala Val Trp Arg lie Asp Thr Pro Asp Lys Leu Thr 1 5 10
  • Trp Gly Ala Val Trp Arg lie Asp Thr Pro Asp Lys Leu Thr 1 5 10

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Abstract

L'invention concerne l'épitope du lymphocyte T immunodominant du ray-grass, sa séquence minimale, son rôle dans le rhume des foins ainsi que son utilisation dans la fabrication d'un médicament destiné au traitement ou à la prophylaxie du rhume des foins. Selon l'invention, on obtient un polypeptide possédant neuf restes d'acides aminés comprenant les six restes VXRIDT, ainsi que des analogues et des mimétiques (répliques) de celui-ci. On peut administrer ce polypeptide en tant que méthode de traitement ou de prophylaxie des allergies, notamment les allergies au ray-grass ou le rhume des foins.
PCT/GB1995/001493 1994-06-24 1995-06-26 Epitopes de lymphocytes t d'allergene du pollen de ray-grass Ceased WO1996000238A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP95922664A EP0772629A1 (fr) 1994-06-24 1995-06-26 Epitopes de lymphocytes t d'allergene du pollen de ray-grass
JP8502928A JPH10506877A (ja) 1994-06-24 1995-06-26 ライグラス花粉アレルゲンのｔ細胞エピトープ
AU27487/95A AU707740B2 (en) 1994-06-24 1995-06-26 T cell epitopes of rye grass pollen allergen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9412714A GB9412714D0 (en) 1994-06-24 1994-06-24 T cill epitopes
GB9412714.9 1994-06-24

Publications (1)

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WO1996000238A1 true WO1996000238A1 (fr) 1996-01-04

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PCT/GB1995/001493 Ceased WO1996000238A1 (fr) 1994-06-24 1995-06-26 Epitopes de lymphocytes t d'allergene du pollen de ray-grass

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EP (1) EP0772629A1 (fr)
JP (1) JPH10506877A (fr)
AU (1) AU707740B2 (fr)
CA (1) CA2193860A1 (fr)
GB (1) GB9412714D0 (fr)
WO (1) WO1996000238A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997046582A1 (fr) * 1996-06-05 1997-12-11 Peptide Therapeutics Limited Vaccin meningococcique
WO2003082924A1 (fr) * 2002-04-02 2003-10-09 Monash University Reactifs immunotherapeutiques et immunoprophylactiques
AU2003213861B2 (en) * 2002-04-02 2010-04-29 Circassia Limited Immunotherapeutic and immunoprophylactic reagents
US8753644B2 (en) 2009-02-05 2014-06-17 Circassia Limited Grass peptides for vaccine

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2520537C (fr) 2003-03-28 2012-01-31 National Institute Of Agrobiological Sciences Procede de production d'un organe de stockage vegetal avec une production elevee de proteines de recombinaison et nouvelle proteine de recombinaison
WO2012026309A1 (fr) * 2010-08-23 2012-03-01 公立大学法人横浜市立大学 Création d'un médicament anticorps anti-pad4

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0403312A1 (fr) * 1989-06-15 1990-12-19 Btg International Limited Peptides immunoactifs et anticorps et leurs utilisations dans le traitement antiallergique

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0403312A1 (fr) * 1989-06-15 1990-12-19 Btg International Limited Peptides immunoactifs et anticorps et leurs utilisations dans le traitement antiallergique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BUNGY ET AL.: "T cell epitopes of the major fraction of rye grass Lolium perenne (Lol p I) defined using overlapping peptides in vitro and in vivo. I. Isoallergen clone1A", CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol. 94, no. 1, OXFORD,GB, pages 111 - 116 *
PEREZ ET AL.: "cDNA cloning and immunological characterization of the rye grass allergen Lol p I", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 265, no. 27, 25 September 1990 (1990-09-25), MD US, pages 16210 - 16215 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997046582A1 (fr) * 1996-06-05 1997-12-11 Peptide Therapeutics Limited Vaccin meningococcique
WO2003082924A1 (fr) * 2002-04-02 2003-10-09 Monash University Reactifs immunotherapeutiques et immunoprophylactiques
AU2003213861B2 (en) * 2002-04-02 2010-04-29 Circassia Limited Immunotherapeutic and immunoprophylactic reagents
US8753644B2 (en) 2009-02-05 2014-06-17 Circassia Limited Grass peptides for vaccine

Also Published As

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AU707740B2 (en) 1999-07-15
AU2748795A (en) 1996-01-19
CA2193860A1 (fr) 1996-01-04
GB9412714D0 (en) 1994-08-17
EP0772629A1 (fr) 1997-05-14
JPH10506877A (ja) 1998-07-07

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