Reduced Virus Load in Rhesus Macaques Immunized with Recombinant gp160 and Challenged with Simian Immunodeficiency Virus

As a safe alternative to inactivated and live-attenuated whole-virus SIV vaccines, we have evaluated the potential of SIV_mac239 gp160 expressed by recombinant vaccinia virus (vSIVgp160) and baculovirus (bSIVgp160) to protectively immunize rhesus macaques against intravenous (iv) infection with pathogenic SIV_mac isolates. Macaques were immunized with live vSIVgp160 and/or bSIVgp160 protein partially purified from insect cells. The challenge viruses, propagated in rhesus peripheral blood mononuclear cells, consisted of the molecular clone SIV_mac239 and another genetically similar, uncloned isolate, SIV_mac251. Although antibodies that bind gp130 were induced in all animals following immunization with SIVgp160, neutralizing antibodies were undetectable 1 week prior to virus challenge. These results differ from those for macaques vaccinated with inactivated, whole SIV. All animals became infected after iv inoculation with 1–10 AID₅₀ of either challenge virus. For animals challenged with SIV_mac251, but not those challenged with SIV_mac239, the cell-free infectious virus load in plasma of vSIVgp160-primed, bSIVgp160-boosted macaques was significantly lower than in unimmunized controls at 2 weeks postchallenge. Virus virulence, immunization regimen, and challenge with homologous or heterologous virus are factors critical to the outcome of the study. Immunization with surface glycoprotein may not necessarily provide protective immunity against infection but may reduce virus load. The relationship between reduction in virus load by vaccination and delay in onset of disease remains to be determined.