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WO1993019775A1 - Administration de liposomes contenant des peptides ou des proteines comportant des determinants antigeniques de ctl de proteines vih - Google Patents

Administration de liposomes contenant des peptides ou des proteines comportant des determinants antigeniques de ctl de proteines vih Download PDF

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Publication number
WO1993019775A1
WO1993019775A1 PCT/US1993/002978 US9302978W WO9319775A1 WO 1993019775 A1 WO1993019775 A1 WO 1993019775A1 US 9302978 W US9302978 W US 9302978W WO 9319775 A1 WO9319775 A1 WO 9319775A1
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WIPO (PCT)
Prior art keywords
peptide
protein
hiv
liposomes
proteins
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/US1993/002978
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English (en)
Inventor
Carl R. Alving
David Cassatt
Scott Koenig
Nabila Wassef
Wendy White
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MedImmune LLC
United States Department of the Army
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MedImmune LLC
United States Department of the Army
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Publication of WO1993019775A1 publication Critical patent/WO1993019775A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/21—Retroviridae, e.g. equine infectious anemia virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • This invention relates to the induction of a T-cell
  • this invention relates to the induction of a CTL response against HIV by administering liposomes containing peptides or proteins including CTL epitopes of HIV proteins.
  • CMI Cell-mediated immunity
  • HIV human immunodeficiency virus
  • AIDS virus HIV vaccines and/or therapies based on the generation of passive transfer of HIV-specific antibody in the absence of cell-mediated immunity have not yielded consistent protection in primates challenged with the HIV virus.
  • immune responses to certain segments of the virus may be deleterious.
  • Such problems associated with the development of vaccines against AIDS virus may be avoided by employing vaccines which include small regions of HIV proteins which are known to produce neutralizing antibody responses or cytotoxic T lymphocyte responses.
  • a potential target for use in a vaccine against HIV is the HIV envelope, or env protein (also referred to as gp 120 or gp 160).
  • the HIV env protein contains several hypervariable regions (or V regions), of which one region, the V3 loop, contains a peptide sequence that is important for the generation of humoral and cellular immune responses.
  • the V3 loop which is defined by a disulfide bond, contains a principal neutralizing determinant (or PND), as antibodies specific for the V3 loop have been shown to neutralize HIV (Rusche, et al., PNAS, Vol. 85, pgs. 3198-3202 (1988); Goudsmit, et al., PNAS. Vol. 85, pgs.
  • a method of inducing in an animal, a CTL response against HIV comprises administering to an animal lipid vesicles, or liposomes including at least one peptide or protein which includes at least one CTL epitope of an HIV
  • the lipid vesicles, or liposomes are administered in an amount effective to induce in an animal a CTL response against HIV.
  • liposomes including at least one peptide or protein which includes at least one CTL epitope of an HIV
  • the peptide or protein which includes a CTL eptiope of an HIV protein may be encapsulated within the liposome, ..or may form a portion of the liposome wall, or may be bound to the liposome wall.
  • the peptide or protein may be bound to the exterior or to the interior of the liposome wall.
  • lipid vesicles including a peptide or protein which includes a CTL epitope of an HIV protein are administered to an animal, an increased CTL response in the animal against HIV is obtained.
  • liposomes are taken up by macrophages, and the peptide contained within them can be presented to T cells or can enter the
  • Peptides or proteins which include CTL epitopes of HIV proteins, and which may be included in the liposomes include, but are not limited to, HIV env (also known as gp 120 or gp 160); HIV-gp 41; HIV pol; HIV nef; HIV gag; HIV tat; HIV rev; HIV vif; HIV vpr; HIV vpu; and HIV vpx, or fragments or derivatives thereof.
  • the peptide or protein is an HIV env protein or fragment or derivative thereof.
  • the peptide or protein is the V3 loop of the HIV env protein gp 120, or a fragment or derivative thereof.
  • the peptide or protein is the P18 peptide of the V3 loop of HIV-III-B env protein.
  • P18 peptide has the following structural formula:
  • the peptide or protein may, in one embodiment, be conjugated with a conjugate peptide or protein prior to being included in the liposome.
  • the conjugate may be attached to the N-terminal or the C-terminal of the peptide or protein.
  • conjugate peptides or proteins include, but are not limited to, ovalbumin.
  • one or more amino acids be attached to the N-terminal or the C-terminal of the peptide or protein prior to attachment of the peptide or protein to the conjugate peptide or protein, and wherein the peptide or protein is attached to the conjugate peptide or protein via the cysteine residue.
  • a cysteine residue or an amino acid chain having a cysteine residue at its N-terminus is attached to the N-terminal of the peptide or protein.
  • a cysteine residue or an amino acid chain having a cysteine residue at its N-terminus is attached to the N-terminal of the peptide or protein.
  • C-terminus is attached to the C-terminal of the peptide or protein.
  • a Cys-Gly (CG) dipeptide is attached to the N-terminal of P18 peptide to form a peptide having the following structural formula:
  • This peptide may then be attached to a conjugate peptide or protein, such as ovalbumin, to form a conjugate such as, for example, ovalbumin-Cys-Gly-P18 peptide.
  • a conjugate peptide or protein such as ovalbumin
  • such peptides or proteins having a cysteine -containing amino acid chain at the N-terrainus or C-terminus may be included in a liposome alone (without being attached to a conjugate peptide or protein) in order to induce a CTL response against HIV.
  • Applicants have found that when a Cys-Gly-P18 peptide contained in a liposome is administered to an animal, that, in addition to a CTL response, an improved humoral immune response against HIV is generated as well. It is to be understood, however, that the scope of the present invention is not to be limited to any particular conjugate peptides or proteins, or to any particular cystein-containing amino acid chains which may be attached to the peptides or proteins of the present invention.
  • the peptides or proteins employed in the present invention may be synthesized by means well-known in the art.
  • the peptides or proteins may be synthesized on an automatic peptide synthesizer. (Merrifield, J. Am. Chem. Soc., Vol. 85, pg. 2149 (1963)).
  • the peptides or proteins may be produced by genetic engineering techniques. For example, there may be provided DNA encoding a peptide or protein which includes a CTL epitope of an HIV protein. The DNA is placed in an appropriate expression vector, which is transformed into an appropriate organism which expresses the peptide or protein.
  • the liposome which includes the peptide or protein may be formed by a variety of methods known to those skilled in the art.
  • the liposome may be formed according to the methods of Alving, et al., Liposome Technology, Gregoriadis, ed., (CRC Press, Boca Raton, Florida) or Fries, et al., PNAS, Vol. 89, pgs. 358-362 (1992).
  • the liposomes may be formed, for example, from one or more lipids and one or more sterols.
  • Lipids which may be employed include, but are not limited to, phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, spingomyelin,
  • phosphatidylethanolaimine phosphatidylinositol
  • phosphatidic acid phosphatidic acid
  • cardiolysin phosphatidylethanolaimine
  • Sterols which may be employed include cholesterol and lanosterol.
  • the liposomes may further include lipid A or a lipopolysaccharide which, along with the above-mentioned lipids and sterols, also becomes incorporated in the liposome wall.
  • the peptides or proteins may, in one embodiment, be encapsulated within the liposomes by a variety of means known to those skilled in the art.
  • a lyophilized lipid film may be reconstituted with a buffer containing the peptides, or proteins, whereby a portion of the peptide or protein becomes encapsulated within the liposome during reconstitution.
  • the present invention has been described with respect to encapsulation of the peptides or proteins within liposomes, it is to be understood that within the scope of the present invention, the peptides or proteins may form part of the liposome wall or may be attached to the liposome wall such that the peptide or protein is attached to the exterior or the
  • composition for inducing in an animal a CTL response against HIV which comprises a lipid vesicle including least one peptide or protein including at least one CTL epitope of an HIV protein.
  • the lipid vesicle, or liposome, and the peptide or protein may be those hereinabove described.
  • the liposomes which include the peptide or protein which includes a CTL epitope of an HIV protein may be employed in a composition, such as a vaccine, for inducing in an animal a CTL response against HIV.
  • the vaccine may be administered to a human or non-human animal.
  • the liposomes may be administered in conjunction with a suitable pharmaceutical carrier.
  • Vehicles for vaccines are well known in the art and the selection of a suitable vehicle is deemed to be within the scope of those skilled in the art from the teachings contained herein. The selection of a suitable vehicle is also dependent upon the manner in which the vaccine is to be administered. Alternatively, because liposomes possess adjuvant properties, the liposomes may be administered without a carrier and instead may be administered in water alone.
  • the vaccine may be in the form of an injectable dose and may be administered intramuscularly, intravenously, orally, intradermally, or by subcutaneous administration.
  • the peptide or protein may be administered to an average human adult in an amount of from about 1 microgram to about 1,500 micrograms, preferably from about 10 micrograms to about 1,000 micrograms.
  • the peptide may be administered for example at monthly intervals for a period of time of about three months. It is to be understood, however, that the scope of the present invention is not to be limited to any particular dosage levels or intervals of administration.
  • Synthetic P18 peptide (SEQ ID NO:1); or P18 peptide having Cys-Gly chain attached to its N-terminus (SEQ ID NO:2), also sometimes hereinafter referred to as CG-P18 was synthesized by using the stepwise solid phase approach of Merrifield, J. Am.
  • acylating species were used as the acylating species for all amino acids except asparagine, glutamine, arginine, and histidine.
  • Ovalbumin (5 mg. or 100 nmole) was dissolved in 1 ml PBS, pH 6.8. To this solution was added 3 mg (10 ⁇ mole) m-male- imidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in 300 ml of synthesis grade dimethyiformamide (DMF). The mixture was allowed to react for one hour at room temperature with gentle mixing. At the end of one hour reaction time, the entire mixture was desalted over a 1cm x 20 cm column packed with Sephadex G-50 equilibrated with 0.1M phosphate buffer, pH 6.0. The eluant was monitored for absorbance at 280 mm, and the derivatized fraction of maleimidobenzyl ovalbumin (OVA-MB) was collected in the void volume (V ).
  • V void volume
  • Cysteine-containing peptides (3 to 5 mg) were dissolved in 1 ml cold 0.1M sodium borate buffer, pH 9.1. To this was added 100 ml of a 0.1M sodium borohydride solution. The reduction was permitted to proceed for 15 min at 4oC. After 15 min excess reducing agent was destroyed by acidifying with 6N hydrochloric acid. Following this the solution containing reduced peptide (either P18 or CG-P18) was returned to neutral pH (pH 6-7) with sodium hydroxide. The reduced peptide was slowly added with stirring to the derivatized protein fraction (OVA-MB) prepared above. This mixture was reacted overnight at room temperature. The conjugation reaction mixture was extensively dialyzed (MWCO 12,000-14,000 daltons) against water at 4°C to remove excess peptide and buffer salts.
  • OVA-MB derivatized protein fraction
  • the number of moles of peptide conjugated per mole OVA was determined by amino acid analysis.
  • the OVA-MB-peptide conjugates and OVA were hydrolyzed separately with 100 ul constant boiling (6N) HCl for 2 hours at 150°C.
  • the hydrolyzates were then dried in vacuo in the presence of potassium hydroxide.
  • the dried-down samples were then resuspended and applied to a Beckman "System Gold" analyzer for determination of the amino acid content. By examining and comparing the ratio of amino acids determined for both the OVA and OVA-MB-peptide the extent of crosslinking was evaluated.
  • Liposomes were prepared as taught by Alving, et al. (in
  • the chloroform was removed with a rotary evaporator and the lipid film further dried in a vacuum dessicator.
  • the resultant lipid film was hydrated with sterile water to a final phospholipid concentration of 50-200 mM and then lyophilized. After lyophilization, liposomes were reconstituted to a
  • PBS phosphate-buffered saline, pH 7.4, (PBS) containing peptide P18, CG-P18, or P18 peptide conjugate.
  • PBS phosphate-buffered saline, pH 7.4,
  • Unencapsulated P18 peptide, CG-P18, or peptide conjugate was removed by washing the liposomes with PBS and washed pellets were resuspended in PBS to a phospholipid concentration of 100-200 mM.
  • the encapsulated peptide or peptide conjugate was determined and the final
  • liposome preparation was diluted appropriately according to the concentration of peptide or peptide conjugate required per injection. Concentration of the peptide or peptide conjugate was measured by hydrolyzing a sample of the liposomes in 6N HCl for 2 hours and examining by amino acid analysis as described above.
  • Preparations for immunization contained peptide (P18 or CG-P18) alone or conjugated to ovalbumin.
  • Peptide was
  • the non-encapsulated peptide or peptide conjugate was administered in PBS with no adjuvant, in PBS emulsified in complete Freund's adjuvant (CFA) for priming, and in incomplete Freund's adjuvant (IFA) for boosting, or adsorbed onto 1.5 mg of aluminum hydroxide (alum).
  • CFA complete Freund's adjuvant
  • IFA incomplete Freund's adjuvant
  • Peptide or peptide conjugate encapsulated in liposomes was administered either in liposomes alone or in liposomes adsorbed with 1.5 mg of alum.
  • mice (4 per group) were given primary immunizations of peptide or peptide conjugate intraperitoneally, and boosting intraperitoneal immunizations 3 weeks later (for the peptide-protein conjugate) or 3 and 11 weeks later (for the peptides).
  • Immulon R flat-bottom plates were coated overnight with 250 ng/well of P18. After washing and blocking with PBS containing 3% dry milk and 0.1% Tween-20, various dilutions of sera diluted in PBS containing 1% goat serum and 0.1% Tween-20 were added and incubated for 1 hour. The plates were washed and goat anti-mouse IgG conjugated to horseradish peroxidase was added and incubated for 1 hour. After washing, substrate solution was added and allowed to develop for 30 min. Readings were taken at a
  • mice immunized with OVA-CG-P18 were tested at 3, 5, 7, and 17 weeks after the initial immunization.
  • mice immunized with P18 peptide or CG-P18 were tested at 7 weeks after the initial immunization.
  • the peptides had been administered without adjuvant, in CFA/IFA, in alum, in liposomes, in liposomes in alum, in liposomes with lipid A, or in liposomes with lipid A in alum.
  • the anti-P18 titers are given in Table II below.
  • CTL cytolytic
  • Spleens from mice immunized with OVA-CG-P18, P18, or CG-P18 were taken and disrupted to make a single cell suspension. Spleen cells were washed and cultured in 25 cm 2 flasks at 5 ⁇ 10 7 cells/flask in a volume of 10 ml. Syngeneic P815 cells were pulsed with 50 ug of P18 for 40 min and then mitomycin C treated for 40 min and added to the flasks at 5 ⁇ 10 6 cells/flask.
  • effector cells were added to 96 well microtiter plates at 5 ⁇ 10 5 , 2.5 ⁇ 10 5 , and 6.25 ⁇ 10 4 cells/well.
  • P815 cells that were pulsed with 35 ug P18 or left unpulsed were loaded with 200 uCi of 51 Cr for 2 hrs. and added to the cultures at 5 ⁇ 10 3 cells/well.
  • P815 cells that were loaded with 51 Cr were cultured alone (to determine spontaneous release) or with 10% sodium dodecyl sulfate (to determine total release). Cells were cultured for 4 hrs. and the supernatants were harvested and counted to determine 51 Cr release. Percent lysis was determined by the following equation:
  • Figure 1 shows the CTL activity of spleens from mice immunize with OVA-CG-P18 conjugate, which was administered as described in Example 5. The spleens were taken 14 weeks after the initial immunization. As shown in Figure 1, maximal CTL response was obtained when the OVA-CG-F18 conjugate was encapsulated in
  • liposomes with lipid A without adsorption of the liposomes to alum.
  • FIG. 2 shows the CTL activity of spleens from mice immunize with Pl ⁇ or CG-P18, which was administered as described in Example 5. The spleens were taken 18 weeks after the initial immunization As shown in Figure 2, mice that received peptide encapsulated in lipsomes containing lipid A were able to mount a CTL response to P18.
  • ADDRESSEE Carella, Byrne, Bain,
  • NAME/KEY P18 peptide derivative
  • xi SEQUENCE DESCRIPTION: SEQ ID NO: 2: Cys Gly Arg Ile Gln Arg Gly Pro Gly Arg

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Abstract

Un procédé permet d'induire chez l'animal une réaction des lymphocytes T cytotoxiques (CTL) contre le VIH. Il comprend l'administration à cet animal de vésicules lipidiques (des liposomes par exemple) qui contiennent au moins un peptide ou une protéine comportant au moins un déterminant antigénique d'un CTL d'une protéine VIH.
PCT/US1993/002978 1992-03-31 1993-03-25 Administration de liposomes contenant des peptides ou des proteines comportant des determinants antigeniques de ctl de proteines vih Ceased WO1993019775A1 (fr)

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Application Number Priority Date Filing Date Title
US86070792A 1992-03-31 1992-03-31
US860,707 1992-03-31

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040243A1 (fr) * 1995-06-07 1996-12-19 U.S. Department Of The Army Liposomes contenant une glycoproteide du virus de l'immunodeficience humaine et leurs procedes d'utilisation
WO2000029008A3 (fr) * 1998-11-17 2000-08-10 Univ Texas Induction de lymphocytes t specifiques du vih
WO2000076537A3 (fr) * 1997-09-10 2001-05-03 Us Health Utilisation de complexes de peptide-lignee cellulaire semi-allogenique§ pour le traitement du cancer, du sida et d'autres maladies virales
FR2806912A1 (fr) * 2000-04-04 2001-10-05 Fond Mondiale Rech Et Preventi UTILISATION DE PROTEINES gp120 ET gp160 MODIFIEES DANS LA BOUCLE V3 DU VIH-1 POUR LA PREPARATION DE COMPOSITIONS VACCINALES ET FORMULATIONS LES CONTENANT

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4871488A (en) * 1985-04-22 1989-10-03 Albany Medical College Of Union University Reconstituting viral glycoproteins into large phospholipid vesicles
EP0339504A2 (fr) * 1988-04-26 1989-11-02 The Du Pont Merck Pharmaceutical Company Virus d'immunodéficience humaine (HIV) peptide env-codé capable de provoquer les anticorps inhibiteurs du HIV dans les mammifères
WO1991004051A1 (fr) * 1989-09-19 1991-04-04 Medimmune, Inc. Peptides comprenant des epitopes ctl de proteines hiv et leur utilisation
US5030449A (en) * 1988-07-21 1991-07-09 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Synthetic vaccine against AIDS virus

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4871488A (en) * 1985-04-22 1989-10-03 Albany Medical College Of Union University Reconstituting viral glycoproteins into large phospholipid vesicles
EP0339504A2 (fr) * 1988-04-26 1989-11-02 The Du Pont Merck Pharmaceutical Company Virus d'immunodéficience humaine (HIV) peptide env-codé capable de provoquer les anticorps inhibiteurs du HIV dans les mammifères
US5030449A (en) * 1988-07-21 1991-07-09 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Synthetic vaccine against AIDS virus
WO1991004051A1 (fr) * 1989-09-19 1991-04-04 Medimmune, Inc. Peptides comprenant des epitopes ctl de proteines hiv et leur utilisation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MOLECULAR IMMUNOLOGY, Volume 27, No. 6, issued 1990, NEURATH et al., "Confronting the Hypervariability of an Immunodominant Epitope Eliciting Virus Neutralizing Antibodies from the Envelope Glycoprotein of the Human Immunodeficiency Virus Type 1 (HIV-1)", pages 539-549. *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040243A1 (fr) * 1995-06-07 1996-12-19 U.S. Department Of The Army Liposomes contenant une glycoproteide du virus de l'immunodeficience humaine et leurs procedes d'utilisation
WO2000076537A3 (fr) * 1997-09-10 2001-05-03 Us Health Utilisation de complexes de peptide-lignee cellulaire semi-allogenique§ pour le traitement du cancer, du sida et d'autres maladies virales
WO2000029008A3 (fr) * 1998-11-17 2000-08-10 Univ Texas Induction de lymphocytes t specifiques du vih
US6656471B1 (en) 1998-11-17 2003-12-02 Board Of Regents, The University Of Texas System HIV-specific T-cell induction
US7306804B2 (en) 1998-11-17 2007-12-11 Board Of Regents, The University Of Texas System HIV-specific T-cell induction
FR2806912A1 (fr) * 2000-04-04 2001-10-05 Fond Mondiale Rech Et Preventi UTILISATION DE PROTEINES gp120 ET gp160 MODIFIEES DANS LA BOUCLE V3 DU VIH-1 POUR LA PREPARATION DE COMPOSITIONS VACCINALES ET FORMULATIONS LES CONTENANT

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