ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study utilized recombinant SVV expressing simian immunodeficiency virus (SIV) antigens to vaccinate rhesus macaque and test for protection against simian AIDS following SIV challenge. Ten rhesus monkeys, divided into two groups of five each, received subcutaneous and intratracheal inoculations/immunizations with SVV-SIVgag and -SIVenv (Grp1) or SVV-RSVG and -RSVM2 (Gp2) at d0 and at 6weeks. Six months after immunization, all animals were intravenously challenged with 100 TCID50 SIVmac251. Although humoral responses to SIV antigens were initially weak in Gp1 animals, following SIV challenge, a rapid augmented response was demonstrated. IFN-g ELISPOT analysis showed specific cellular responses against SIVgp130 in 2 of 5 animals in Gp1 only. Animals also monitored for circulating SIV bDNA showed a trend towards lower viral loads in Gp1 animals compared with Gp2 control animals. Mann Whitney analysis showed significantly lower mean viral loads in Grp1 compared with Gp2 at d14 peak viremia: log 6.8 +/-0.2 and log 7.5 +/-0.4 (p=0.016); and d56 viral set point: log5.3+/-0.5 and log and log6.3+/-0.7 (p=0.03), respectively. These results demonstrate that recombinant varicella/SIV vaccines can stimulate humoral and cellular immune responses against SIVmac antigens in the rhesus macaque. Following SIV challenge, circulating SIV viral loads were significantly lower as compared to controls, vaccinated with an unrelated viral gene, suggesting their potential in protection against simian acquired immunodeficiency syndrome.