Characterization of Immune Responses Elicited in Macaques Immunized Sequentially with Chimeric VEE/SIN Alphavirus Replicon Particles Expressing SIVGag and/or HIVEnv and with Recombinant HIVgp140Env Protein

In the present study, macaques were coimmunized with VEErep/SINenv chimeric alphavirus replicon particles expressing SIVp55Gag and HIVΔV2gp140Env or only with replicon particles expressing HIVΔV2gp140Env. All animals were subsequently immunized with recombinant trimeric HIVΔV2gp140Env protein. During alphavirus immunization, anti-SIVGag and anti-HIVEnv-specific interferon (IFN)-γ responses, as well as high titers of anti-HIVEnv binding (gp120 but not gp41 specific) and anti-HIV neutralizing antibodies, were generated. The subsequent immunization with recombinant HIVΔV2gp140 enhanced the neutralizing antibody titers and Env-specific IFN-γ responses. Following intravenous challenge with the R5- tropic SHIV_SF162P4 virus, significantly lower primary plasma viremia levels were recorded in the immunized animals, as compared to control animals immunized with replicon particles expressing influenza virus HA. Our results show that this method of immunization elicits both strong cellular immunity and neutralizing antibodies in primates and, thus, merits further investigation.