ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究利用表达猴免疫缺陷病毒（SIV）抗原的重组SVV疫苗接种恒河猴，并测试SIV攻击后对猴艾滋病的保护作用。 10只恒河猴分为两组，每组5只，分别在d 0和6周时接受SVV-SIVgag和-SIVenv（Grp 1）或SVV-RSVG和-RSVM 2（Gp 2）皮下和皮下接种/免疫。 免疫后6个月，用100 TCID 50 SIVmac 251静脉内攻击所有动物。 虽然体液反应SIV抗原最初在Gp 1动物弱，SIV攻击后，一个快速增强的反应被证明。 IFN-g ELISPOT分析显示，仅Gp 1组5只动物中有2只出现针对SIVgp 130的特异性细胞应答。 还监测了动物的循环SIV bDNA，与Gp 2对照动物相比，Gp 1动物的病毒载量呈降低趋势。Mann Whitney分析显示，与Gp 2相比，第14天病毒血症峰值时Grp 1的平均病毒载量显著较低：log 6.8 +/-0.2和log 7.5 +/-0.4（p=0.016）;第56天病毒设定点分别为log 5.3 +/-0.5和log 6.3 +/-0.7（p=0.03）。 这些结果表明，重组水痘/SIV疫苗可以刺激恒河猴对SIVmac抗原的体液和细胞免疫应答。 SIV攻击后，循环SIV病毒载量显着低于对照组，接种无关的病毒基因，这表明它们在保护猴获得性免疫缺陷综合征的潜力。

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.