Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/ simian–human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag- specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immuniza...