Induction of high levels of epitope-specific antibodies by epitope/peptidecandidate vaccines against human immunodeficiency virus type-1 (HIV-1)

To test the immunogenicity of GPGRAFY-epitope-based candidate vaccines, a p eptide with four repetitive GPGRAFY epitopes, V3-P1 [C-(GPGRAFY)(4)], and a peptide (PND) of the principal neutralizing domain (V3 loop: amino acid 30 1-328: C-TRPNNNTRKSIRIQRGPGRAFYTIGKI) on gp120 were synthesized and covalen tly coupled to a carrier protein BSA, Immunization of BALB/c mice and New Z ealand White Rabbits with these conjugate vaccines engendered strong antibo dy responses against the PND (mouse serum titer by 1:12,800-25,600; rabbit serum titer by 1:6,400-12,800). Interestingly, the V3-P1-BSA conjugates and the PND-BSA conjugates could induce high levels of GPGRAFY-epitope-specifi c antibodies in the mice and rabbits (mouse serum titer by 1:25,600; rabbit serum titer by 1:12,800-25,600), while a recombinant gp160 subunit vaccine induced a low level of GPGRAFY-epitope-specific antibodies (serum titer by 1:400-1,600 in mice and rabbits), To confirm the above results, GPGRAFY-ep itope-specific antibodies were isolated from rabbit sera induced by V3-P1-B SA, PND-BSA conjugates and rgp160 vaccine. In fact, 23-38 and 13-22 mu g ep itope-specific antibodies per milliliter serum were isolated from rabbit se ra induced by V3-P1-BSA and PND-BSA conjugate, respectively, while 1.34 mu g epitope-specific antibodies per milliliter serum were identified in rabbi t serum induced by rgp160 vaccine, In the control group, only 0.069 mu g pr oteins per milliliter serum were found in pooled pre-immune serum (normal s erum). These results from mouse and rabbit experiments indicate that epitop e and peptide vaccines both induce high levels of GPGRAFY-epitope-specific antibodies in comparison with rgp160 subunit vaccine, suggesting that epito pe/peptide vaccines may be a new strategy to induce protective activity.