DEVELOPMENT OF A NONHUMAN PRIMATE MODEL FOR VARICELLA AND HERPES ZOSTER

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。 由于世界人口的寿命在增加，免疫衰老引起的健康并发症无疑也将增加。其中这些并发症是带状疱疹（带状疱疹）引起的水痘带状疱疹病毒的重新激活。目前批准的带状疱疹疫苗（来自Merck的ZosterVax）将带状疱疹的发病率降低了50%。因此，50%的这一人群仍然容易患带状疱疹及其随之而来的神经系统并发症。提高这种疫苗的有效性和安全性的研究需要更好地了解疾病不同阶段对VZV的免疫反应。然而，这些研究是复杂的，因为目前还没有一种实验动物模型，可以概括急性（水痘，水痘）和复活（带状疱疹）形式的疾病。另一种方法是利用非人灵长类动物（NHP）模型，该模型易受密切相关的病毒猿猴水痘病毒（SVV）感染。实际上，SVV和VZV之间相当大的临床和分子相似性表明NHP的SVV感染作为动物模型具有相当大的潜力。 我们最近发现，恒河猴感染SVV重演了人类VZV感染的特征，包括：水痘皮疹的发展，体液和细胞免疫，急性病毒血症的解决和建立潜伏期的感觉神经节。这种新的模型将允许更深入地了解老年受试者中VZV再激活的免疫缺陷，这反过来将有助于设计有效的疫苗来增强VZV免疫监视的特定方面。

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. Since the life span of the world population is increasing, health complications as a result of immune senescence will undoubtedly increase as well. Amongst these complications is herpes zoster (shingles) caused by the reactivation of Varicella Zoster Virus. The currently approved zoster vaccine (ZosterVax from Merck) reduces the incidence of herpes zoster by 50%. Therefore, 50% of this population remains susceptible to zoster and its ensuing neurological complications. Studies to improve the efficacy and safety of this vaccine require an improved understanding of the immune response to VZV during different stages of the disease. However, these studies are complicated since an experimental animal model that can recapitulate both the acute (varicella, chickenpox) and reactivation (zoster) forms of the disease is currently not available. An alternative is to utilize a nonhuman primate (NHP) model that is susceptible to infection by the closely related virus Simian varicella virus (SVV). Indeed, considerable clinical and molecular similarities between SVV and VZV indicate that SVV infection of NHP has considerable potential as an animal model. We have recently shown that infection of rhesus macaques with SVV recapitulates the hallmarks of VZV infection in humans including: the development of varicella rash, humoral and cellular immunity, resolution of acute viremia and the establishment of latency in sensory ganglia. This novel model will allow a deeper understanding of the immune deficiencies that underlie VZV reactivation in elderly subjects, which in turn will facilitate the design of efficacious vaccines to boost specific aspects of VZV immune surveillance.