Induction of high levels of epitope-specific antibodies by epitope/peptide candidate vaccines against human immunodeficiency virus type-1 (HIV-1).
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 13-22 microg epitope-specific antibodies per milliliter serum were isolated from rabbit sera induced by V3-P1-BSA and PND-BSA conjugate, respectively, while 1.34 microg epitope-specific antibodies per milliliter serum were identified in rabbit serum induced by rgp160 vaccine. In the control group, only 0.069 microg 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.
Yu
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T
Laboratory of Immunology, Research Center for Medical Science and the School of Life Science and Engineering, Tsinghua University, Beijing, PR China.
Bai
Y
Y
Dierich
M P
MP
Chen
Y H
YH
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D010455:Peptides