Comprehensive mapping of SIVmac239 envelope antigenic determinants recognized by specific polyclonal antibodies in vaccinated and/or infected macaques (P4503)

Abstract

Abstract The RV144 trial in Thailand has demonstrated a modest level of protection against HIV infection, which was likely related to V2-binding antibodies. Along with several HIV bnAbs identified recently, it is of great importance to understand the major differences between vaccination and infection in eliciting humoral immune responses. We adopted a robust mapping technique for quantitative measurement of antigenic domains of entire SIV env displayed on the yeast. The finding of reactive determinants ranges from 30 to 240 amino acids, which allows some conformational domains being evaluated as a major technical improvement. The antigen profile of all the tested sera shared two dominant domains: V1V2 stem of gp120 and ecto-gp41 region. A major distinct domain, however, was identified near the V3 loop and the main CD4 binding region which was only recognized by the effective immunized serum but not of the non-effective immunized one. Notably, binding titer of V1V2 antibodies is significantly different between the two vaccination groups, suggested a likely role of these antibodies in controlling viral replication. Unexpectedly, the anti-V1V2 antibody responses were shifted to the ecto-gp41 region when infected macaques developed AIDS. In conclusion, our findings have significant implications to help understanding the humoral immunity against neutralization-resistant SIVmac239 infection and simian AIDS, and to guide rational vaccine immunogen identification and design.