EFFECT OF NATURAL HIV-1 ENVELOPE V1-V2 SEQUENCE DIVERSITY ON THE BINDING OF V3-SPECIFIC AND NON-V3-SPECIFIC ANTIBODIES

In past years, much attention has been paid to the HIV-1 envelope (env ) protein variable region 3 (V3), termed the principal neutralizing de terminant. HIV-1 vaccines were often designed to target V3, and vaccin e efficacy was often measured with V3-based assays. Thus, some disappo intment resulted when volunteers in first clinical vaccine trials gene rated V3-specific antibodies that could not protect against V3-similar viruses. We describe an analysis of V1 and V2 sequence effects on ant ibody binding to V3 and non-V3 determinants. This study involved the p reparation of seven full-length (gp160), chimeric env proteins in a va ccinia virus (VV) expression system. Chimeric proteins displayed diffe rent V1-V2 sequences but were otherwise identical. A panel of 12 monoc lonal antibodies was then tested for binding activities toward the sev en chimeras. Results showed that V1-V2 sequences affected antibody bin ding to env, both in V3 and non-V3 positions. These data demonstrate t he enormous complexity of HIV-1 env protein conformation and antigenic determinants. Respect for the complexity of antibody-antigen interact ions encourages the design of sophisticated immunoglobulin and protein cocktails for use in HIV-1 therapies and vaccines, respectively.