Induction of High Levels of Epitope-Specific Antibodies by Epitope/Peptide Candidate Vaccines against Human Immunodeficiency Virus Type-1 (HIV-1)

抄録

To test the immunogenicity of GPGRAFY-epitope-based candidate vaccines, a peptide with four repetitive GPGRAFY epitopes, V3-P1 [C-(GPGRAFY)₄], and a peptide (PND) of the principal neutralizing domain (V3 loop: amino acid 301-328: C-TRPNNNTRKSIRIQRGPGRAFYTIGKI) on gp120 were synthesized and covalently coupled to a carrier protein BSA. Immunization of BALB/c mice and New Zealand White Rabbits with these conjugate vaccines engendered strong antibody 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-specific 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-epitope-specific antibodies were isolated from rabbit sera induced by V3-P1-BSA, PND-BSA conjugates and rgp160 vaccine. In fact, 23-38 and 13-22μg epitope-specific antibodies per milliliter serum were isolated from rabbit sera induced by V3-P1-BSA and PND-BSA conjugate, respectively, while 1.34μg epitope-specific antibodies per milliliter serum were identified in rabbit serum induced by rgp160 vaccine. In the control group, only 0.069μg proteins per milliliter serum were found in pooled pre-immune serum (normal serum). These results from mouse and rabbit experiments indicate that epitope and peptide vaccines both induce high levels of GPGRAFY-epitope-specific antibodies in comparison with rgp160 subunit vaccine, suggesting that epitope/peptide vaccines may be a new strategy to induce protective activity.