Rhesus macaques vaccinated with consensus envelopes elicit partially protective immune responses against SHIV SF162p4 challenge

The development of a preventative HIV/AIDS vaccine is challenging due to the diversity of viral genome sequences, especially in the viral envelope (Env(160)). Since it is not possible to directly match the vaccine strain to the vast number of circulating HIV-1 strains, it is necessary to develop an HIV-1 vaccine that can protect against a heterologous viral challenge. Previous studies from our group demonstrated that a mixture of wild type clade B Env(gp160s) were able to protect against a heterologous clade B challenge more effectively than a consensus clade B Env(gp160) vaccine. In order to broaden the immune response to other clades of HIV, in this study rhesus macaques were vaccinated with a polyvalent mixture of purified HIV-1 trimerized consensus Env(gp140) proteins representing clades A, B, C, and E. The elicited immune responses were compared to a single consensus Env(gp140) representing all isolates in group M (Con M). Both vaccines elicited anti- Env(gp140) IgG antibodies that bound an equal number of HIV-1 Env(gp160) proteins representing clades A, B and C. In addition, both vaccines elicited antibodies that neutralized the HIV-1(SF162) isolate. However, the vaccinated monkeys were not protected against SHIV(SF162p4) challenge. These results indicate that consensus Env(gp160) vaccines, administered as purified Env(gp140) trimers, elicit antibodies that bind to Env(gp160s) from strains representing multiple clades of HIV-1, but these vaccines did not protect against heterologous SHIV challenge.