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 S IV vaccines, we have evaluated the potential of SIVmac239 gp160 expres sed by recombinant vaccinia virus (vSIVgp160) and baculovirus (bSIVgp1 60) to protectively immunize rhesus macaques against intravenous (iv) infection with pathogenic SIVmac isolates. Macaques were immunized wit h live vSIVgp160 and/or bSIVgp160 protein partially purified from inse ct cells. The challenge viruses, propagated in rhesus peripheral blood mononuclear cells, consisted of the molecular clone SIVmac239 and ano ther genetically similar, uncloned isolate, SIVmac251. Although antibo dies that bind gp130 were induced in all animals following immunizatio n with SIVgp160, neutralizing antibodies were undetectable 1 week prio r to virus challenge. These results differ from those for macaques vac cinated with inactivated, whole SIV. All animals became infected after iv inoculation with 1-10 AID(50) of either challenge virus. For anima ls challenged with SIVmac251, but not those challenged with SIVmac239, the cell-free infectious virus load in plasma of vSIVgp160-primed, bS IVgp160-boosted macaques was significantly lower than in unimmunized c ontrols at 2 weeks postchallenge. Virus virulence, immunization regime n, and challenge with homologous or heterologous virus are factors cri tical to the outcome of the study. Immunization with surface glycoprot ein 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 deter mined.