Fine specificity of anti-V3 antibodies induced in chimpanzees by HIV candidate vaccines

The fine specificity of the anti-V3 antibody responses induced in chimpanzees immunized by various human immunodeficiency type 1 (HIV-1) candidate vaccines and challenged by heterologous strains of HIV-1 was analyzed by enzyme-linked immunosorbent assay (ELISA) and Pepscan epitope mapping. Two chimpanzees immunized with the recombinant canarypox virus ALVAC-HIV (vCP125) expressing gp160MN and boosted with purified gp160MN/LAI alone, then with both immunogens in combination, were not protected against challenge with HIV-1 SF2. Their sera mainly recognized one epitope of the V3 loop, located in the NH2-terminal half. By contrast, immunization of two other chimpanzees with purified gp160MN/LAI and boosting with a synthetic V3MN peptide elicited a strong anti-V3 antibody response with a broader specificity directed against multiple epitopes all along the V3 loop. These chimpanzees were protected against infection by HIV-1 SF2. However, when these two chimpanzees were challenged later with a HIV-1 clade E strain virus, they became infected. We failed to detect any reactivity with the peptide of the ectodomain of gp41 of sera harvested after immunization with the various immunogens or after challenge with HIV-1 SF2 or HIV-1 90CR402. These results demonstrated that anti-V3 antibodies with a restricted fine specificity were induced in chimpanzees immunized with gp160 purified or expressed by recombinant canarypox confirming our previous results obtained in three different species (human, guinea pig and, macaque). In contrast, a boost with the V3 peptide broadened antibody responses, suggesting that the mode of presentation of the V3 loop to the immune system strongly influences the epitope specificity of the resulting antibody response.