Macromolecular assemblage in the design of a synthetic AIDS vaccine.
We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.
Defoort
J P
JP
Rockefeller University, New York, NY 10021.
Nardelli
B
B
Huang
W
W
Ho
D D
DD
Tam
J P
JP
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D014614:Vaccines, Synthetic