Antigen-specific immunoglobulin responses correlate with plasma viral load in SIV/SHIV infected controller macaques (P3049)

There is increasing evidence suggesting an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional B cell epitopes for HIV is also important for developing preventative and therapeutic strategies. We therefore explored the antigen-specific immune responses following SIV or SHIV infection in rhesus macaques to determine functional B cell epitopes and identify factors that may influence control of plasma viremia. Functional B cell epitopes are a minimum of 10 amino acids in length for SIV and occur in similar regions despite differences in the route of mucosal SIV inoculation. Peptide-specific IgG responses generate primarily against gp41, V1-V3 regions of gp120, and the NC and p6 regions of Gag. Controller macaques showed much greater IgG responses to Nef, Tat, and p15 and p27 regions of Gag protein compared to absent or minimal responses in non-controller macaques. Antigen-specific IgM and IgA responses share similar epitopes to that of IgG, however the responses are much more limited. Moreover, antigen-specific IgA responses did not correlate with plasma viremia. Our study has shown that Env-specific IgG responses are not reliable prognostic indicators, unlike Gag, Nef, and Tat-specific IgG responses for SIV/SHIV controllers. Therefore, generation of early functional Gag, Nef and Tat-specific IgG responses may be important therapeutic strategies for the control or prevention of HIV/AIDS.