ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。猴水痘病毒（SVV）感染灵长类动物的临床、病理、免疫学和病毒学特征与人类水痘-带状疱疹病毒感染相似。水痘带状疱疹病毒（VZV）导致水痘（水痘）儿童。在原发性疾病消退后，病毒在神经节中建立潜伏感染，并可能在以后的生活中重新激活，特别是在老年人中。已经使用猿猴对应病毒猿猴水痘病毒SVV开发了猿猴疾病模型，SVV在非人灵长类动物中感染并产生水痘，类似于在VZV和人类中观察到的。已知VZV感染非人灵长类动物，但它不会引起疾病。 进行了一项非人灵长类动物实验，以测试由Dr. Gray构建的SVV-SIVgag和SVV-SIVenv重组病毒在AGM（一种对SVV感染高度敏感的物种）体内的SIV基因表达和免疫原性。9只非洲绿色猴子（AGM）从外部供应商处购买，被隔离，当它们从隔离中释放时，卡特里娜飓风袭击了。我们推迟了这个实验的开始，但最终在2005年11月下旬开始了。 将动物分成四组，分别接种SVV-SIVgag、SVV-SIVenv、gag和env重组体，最后接种野生型SVV作为对照。在两周内，所有动物都出现急性水痘感染的迹象，然后感染消退。6周后，对动物进行加强免疫，并再次随访，但未显示急性感染迹象。我们继续对这些动物进行体格检查和组织取样，以监测临床参数、病毒血症和免疫应答。如通过免疫沉淀反应所确定的，在加强接种后，用SVV-SIV重组病毒免疫的所有动物产生针对SIV gag、env或这两种基因的抗体。Elispot评估显示IFN？g仅使用SVV-SIVenv生产。我们正在继续最终确定和分析研究结果。

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. Simian varicella virus (SVV) infection in primates shares clinical, pathological, immunological, and virological features with varicella-zoster virus infection of humans. Varicella zoster virus (VZV) causes varicella (chicken pox) in children. Following resolution of the primary disease, the virus establishes latent infection in neural ganglia and may reactivate later in life, particularly in the elderly. A simian model of disease has been developed using the simian counterpart virus, simian varicella virus, SVV, which infects and produces varicella in nonhuman primates similarly to that observed for VZV and humans. VZV is known to infect nonhuman primates, however, it does not cause disease. A nonhuman primate experiment was conducted to test SVV-SIVgag and SVV-SIVenv recombinant viruses constructed by Dr. Gray for expression and immunogenicity of the SIV genes in vivo in the AGM, a species highly susceptible to infection with SVV. 9 African green monkeys (AGM) were purchased from an outside vendor, quarantined, and upon their release from quarantine, Hurricane Katrina hit. We were delayed in starting this experiment but finally began in late November, 2005. Animals were divided into four groups for inoculation with either SVV-SIVgag, SVV-SIVenv, both gag and env recombinants, and finally the wild type SVV as control. Within two weeks, all animals had signs of acute varicella infection and then resolved their infection. After 6 weeks, the animals were then boosted and again followed but did not show signs of acute infection. We continued to follow these animals with physical exams, and tissue sampling to monitor clinical parameters, viremia and immune responses. As determined by immunoprecipitation reactions, following the booster vaccination, all animals immunized with the SVV-SIV recombinant viruses generated antibodies to either the SIV gag, env, or both genes. Elispot evaluations showed IFN?g production with the SVV-SIVenv only. We are continuing to finalize and analyze the study results.