ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。灵长类猴水痘病毒（SVV）感染与人类水痘-带状疱疹病毒感染具有相同的临床、病理、免疫学和病毒学特征。水痘带状疱疹病毒（VZV）引起儿童水痘（水痘）。在原发疾病消退后，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。已经利用类人猿对应病毒类人猿水痘病毒（SVV）建立了一种类人猿疾病模型，该病毒在非人类灵长类动物中感染并产生水痘，与在VZV和人类中观察到的情况类似。已知VZV会感染非人类灵长类动物，但它不会引起疾病。在非人类灵长类动物实验中，Gray博士构建了SVV- sivgag和SVV- sivenv重组病毒，在高度易感染SVV的AGM中进行了SIV基因的体内表达和免疫原性测试。9只非洲绿猴（AGM）是从外部供应商那里购买的，并被隔离，当它们从隔离中释放出来时，卡特里娜飓风袭击了。我们推迟了实验的开始，但终于在2005年11月底开始了。将动物分为四组，分别接种SVV- sivgag、SVV- sivenv、gag和env重组体，最后以野生型SVV为对照。在两周内，所有动物都出现了急性水痘感染的症状，然后感染消失了。6周后，对这些动物进行刺激和再次跟踪，但没有出现急性感染的迹象。我们继续对这些动物进行身体检查和组织取样，以监测临床参数、病毒血症和免疫反应。通过免疫沉淀反应确定，在加强疫苗接种后，所有接种了SVV-SIV重组病毒的动物都产生了SIV gag、env或两种基因的抗体。Elispot检测显示IFN？仅使用SVV-SIVenv生产。我们正在继续完成和分析研究结果。

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.