Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 15 to 23 amino acid residues in defined sequence
Patent
1992-07-06
1996-01-02
Woodward, Michael P.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
15 to 23 amino acid residues in defined sequence
435 5, 4351723, 4242081, 4242041, C07K 500, A61K 3912, C12Q 170, C12N 1500
Patent
active
054809673
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention concerns peptide fragments of HIV (human immunodeficiency virus) and the use thereof in a potential vaccine against AIDS (acquired immune deficiency syndrome), and for diagnostic and therapeutic purposes.
BACKGROUND TO THE INVENTION
European Patent Specification No. 0346022 discloses and claims, inter alia, a peptide having the amino acid sequence of a fragment of HIV which interacts specifically with a particular human leucocyte antigen (HLA) class I molecule, to stimulate cytotoxic T lymphocyte immunity.
One such peptide specifically disclosed in the prior application has the sequence NH.sub.2 -lysine-arginine-tryptophan-isoleucine-isoleucine-leucine-glycine-leucine- asparagine-lysine-isoleucine-valine-arginine-methionine-tyrosine-cysteine-C OOH (SEQ ID NO:1), which is derived from the gag (group associated antigen) p24 protein of HIV (ie one of the internal core proteins) between residues 263 and 277, and is known as p24-14. The carboxy-terminal cysteine is not part of the gag sequence and is added to facilitate chemical coupling reactions. This peptide interacts specifically with HLA B27, and individuals with HLA B27 (about 7% of the Caucasian population) should respond to the peptide, resulting in production of cytotoxic T lymphocytes (CTL) specific for gag and HLA B27, and capable of lysing cells infected with HIV.
The present application concerns further such peptides which have now been identified.
SUMMARY OF THE INVENTION
According to one aspect of the present invention there is provided a peptide having the amino acid sequence of a fragment of HIV which interacts specifically with a particular human leucocyte antigen (HLA) class I molecule, to stimulate cytotoxic T lymphocyte immunity, the peptide having the sequence NH.sub.2 -valine-glutamine-asparagine-alanine-asparagine-proline-aspartic acid-cysteine-lysine-threonine-isoleucine-leucine-lysine-alanine-leucine-t yrosine-COOH (SEQ ID NO:2).
This sequence is derived from the gag p24 protein of HIV. This peptide, which is known as p24-20, interacts specifically with HLA B8 and individuals with HLA B8 (about 15% of the Caucasian population) should respond to the peptide, resulting in production of cytotoxic T lymphocytes (CTL) specific for gag and HLA B8, and capable of lysing cells infected with HIV. Peptide p24-20 has also been recognised by a seropositive donor of the HLA type HLA-A3, 29B44, 14 and therefore can be recognised in association with one of these HLA molecules as well as HLA-B8.
According to another aspect of the present invention there is provided a peptide having the amino acid sequence of a fragment of HIV which interacts specifically with a particular human leucocyte antigen (HLA) class I molecule, to stimulate cytotoxic T lymphocyte immunity, the peptide having the sequence NH.sub.2 -cysteine-glycine-serine-glutamic acid-glutamic acid-leucine-arginine-serine-leucine-tyrosine-asparagine-threonine-valine- alanine-threonine-leucine-COOH (SEQ ID NO:3).
This sequence is derived from the gag p17 protein of HIV. This peptide, which is known as p17-8, interacts specifically with HLA A2 and individuals with HLA A2 (about 40% of the Caucasian population) should respond to the peptide, resulting in production of cytotoxic T lymphocytes (CTL) specific for gag and HLA A2, and capable of lysing cells infected with HIV.
According to another aspect of the present invention there is provided a peptide having the amino acid sequence of a fragment of HIV which interacts specifically with a particular human leucocyte antigen (HLA) class I molecule, to stimulate cytotoxic T lymphocyte immunity, the peptide having the sequence NH.sub.2 -cysteine-leucine-arginine-proline-glycine-glycine-lysine-lysine-leucine-l ysine-histidine-isoleucine-valine-COOH (SEQ ID NO:4).
This sequence is derived from the gag p17 protein of HIV. The amino terminal cysteine is not part of the gag sequence and is added to facilitate chemical coupling reactions. The invention thus also includes within its scope the peptide without the amino
REFERENCES:
patent: 4629783 (1986-12-01), Cosand
Greene, 1993, "AIDS and The Immune System" Scientific American Sep., 1993 pp. 99-105.
Brown, 1993, "AIDS Vaccine Trials Viewed With Caution" The Washington Post Newspaper Jun. 10, 1993.
Nixon, et al, 1988, "HIV-1 gag-specific cytotoxic T lymphocytes . . . " Nature 336:484-487.
Immunology, vol. 67, 1989, T. Mathiesen et al: "Mapping of IgG subclass and T-cell epitopes on HIV proteins by synthetic peptides", see pp. 453-459.
Journal of Acquired Immune Deficiency Syndromes, vol. 4, 1989, B. Wahren et al: "HIV-1 Peptides Induce a Proliferative Response in Lymphocytes from Infected Persons", see pp. 448-456.
Dialog Information Services, File 157, AIDSLine, Accssion No. 01344489, Parekh B. S. et al.: "Antigenic analysis of HIV-1 major capsid protein, p. 24", Int Conf AIDS Jun. 4-9 1989, 5 p 651.
AIDS, vol. 3, No. 12, 1989, R. Bridget Ferns et al: "Epitope location of 13 anti-gag HIV-1 monoclonal antibodies using oligopeptides and their cross reactivity with HIV-2", see pp. 829-834.
Gotch Frances M.
McMichael Andre J.
Nixon Douglas F.
Townsend Alain R. M.
Smith L. F.
United Biomedical Inc.
Woodward Michael P.
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