ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他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。 SVV重组表达猴免疫缺陷病毒（SIV）抗原用于疫苗接种恒河猴在疫苗/攻击实验。将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）的皮下和皮下接种/免疫。免疫后6个月，用100 TCID 50 SIVmac 251静脉内攻击所有动物。 在攻毒后第14天，与SVV-RSV接种动物相比，SVV-SIV接种动物的病毒载量降低，并在攻毒后258天内持续显著增加。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）。 在该接种组与对照组中记录了对SIV抗原的体液和细胞应答。最令人感兴趣的是，当针对H9生长的SIVmac 251而不是SIVmac 239进行测试时，与对照动物相比，在接种疫苗的动物中产生中和抗体。我们正在努力分子克隆SIVmac 251-CX-1假型病毒，以解释中和的性质。这些结果表明，重组水痘/SIV疫苗可以刺激体液，细胞，和中和免疫反应对SIVmac抗原的恒河猴，并建议这种SVV-SIV重组体的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. An SVV recombinant expressing simian immunodeficiency virus (SIV) antigens was used to vaccinate rhesus macaques in a vaccine/challenge experiment. Ten rhesus monkeys, divided into two groups of five animals 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. Virus loads, were reduced in SVV-SIV vaccinated animals compared with SVV-RSV vaccinated animals at d14 post challenge and continued to increase in significance through 258 days following challenge. 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. Humoral and cellular responses to SIV antigens were documented in this vaccinated group versus the control group. Most intriguing was the production of neutralizing antibodies in the vaccinated animals compared with control animals when tested against H9 grown SIVmac251 but not SIVmac239. We are making efforts to molecularly clone SIVmac251-CX-1 pseudotyped viruses to explain the nature of the neutralization. These results demonstrate that recombinant varicella/SIV vaccines can stimulate humoral, cellular, and neutralizing immune responses against SIVmac antigens in the rhesus macaque and suggest the potential of this SVV-SIV recombinant for protection against simian acquired immunodeficiency syndrome.