ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究利用表达猴免疫缺陷病毒(SIV)抗原的重组SVV免疫恒河猴，并对SIV攻击后的恒河猴艾滋病进行免疫保护试验。将10只恒河猴随机分为两组，每组5只，分别于d0和6周时分别用SVV-SIVgag和-SIVenv(Grp1)或SVV-RSVg和-RSVM2(GP2)皮下和气管内接种/免疫。免疫后6个月，所有动物均经静脉注射100 TCID50 SIVmac251。尽管Gp1动物最初对SIV抗原的体液反应较弱，但在SIV攻击后，体液反应迅速增强。干扰素-g ELISPOT分析显示，仅在Gp1的5只动物中有2只显示了针对SIVgp130的特异性细胞反应。还监测循环SIV BDNA的动物显示，与GP2对照组动物相比，Gp1动物的病毒载量有降低的趋势。Mann Whitney分析显示，在病毒血症d14高峰期，GRP1的平均病毒载量显著低于GP2：log6.8+/-0.2和log7.5+/-0.4(p=0.016)；d56病毒设定点：log5.3+/-0.5和log6.3+/-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反应。在SIV攻击后，循环SIV病毒载量显著低于对照组，接种了无关病毒基因，表明它们在预防猿类获得性免疫缺陷综合征方面具有潜力。

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.