Strong immunogenicity of a multicomponent peptide vaccine developed with the branched lysine oligopeptide method for human immunodeficiency virus infection.

We synthesized one V3 peptide each from HTLV-IIIB, Thai A and Thai B, conjugating them to the T cell epitope of the env region, and we also synthesized a p17 protein peptide of the gag region (HGP-30). These peptides were then coupled to 8-lysine copolymers using N-succinimidyl maleimido carboxylate (M(r) = ca 60,000). We designated this the branched lysine oligopeptide method. The large peptide complexes constructed from these four macromolecular peptides were used with aluminium hydroxide or complete Freund's adjuvant to immunize mice and rabbits four times. ELISA assay showed high titres of anti-peptide antibodies to each V3 loop peptide and the HGP-30 peptide. Strong inhibition of CD4+ dependent cell fusion was obtained with these antisera when IIIB, Thai A and Thai B strains of the human immunodeficiency virus (HIV) were used. Strong anti-fusion inhibition was also observed with two other HIV strains. In addition, an increase of the anti-HIV effect was observed when we used sera obtained by multicomponent vaccine immunization. The same kind of inhibition was also observed in p24 assay systems using these immunized antisera. Activation of IL-2 production in lymphocytes was observed in mice immunized with this vaccine. These results suggest that immunization with macromolecular peptide complexes can result in strong immunogenicity towards HIV-1.