ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

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， 因此可以在其他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。 水痘带状疱疹病毒（VZV）引起水痘（水痘），一种常见的儿童疾病。 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，引起带状疱疹（带状疱疹）和带状疱疹后神经痛。 VZV感染引起显著的发病率，特别是在儿童、老年人和免疫抑制患者中。 目前使用的VZV Oka疫苗对健康儿童和易感成人的免疫接种是安全有效的。 然而，这种疫苗通常不推荐用于某些患者，包括那些免疫功能低下的个体。 该疫苗在宿主神经节中建立潜伏感染，并可能对引起带状疱疹产生反应。 由于需要合适的动物模型，评估这些不足的研究有限。 已经使用猴对应病毒猴水痘病毒SVV开发了水痘疾病的猴模型，SVV感染非人灵长类动物并产生急性感染，其临床、病理学、免疫学和病毒学特征与人的VZV感染相似。 进行了疫苗研究，结果表明，在非人灵长类动物中皮下接种VZV时未显示复制，且未提供针对SVV的交叉反应性保护，而类似的皮下接种SVV显示细胞和体液应答。 潜伏期后，SVV表达有限。潜伏相关转录本（LAT），重叠和反义SVV基因61（HSV-1 ICP 0同源物），SVV基因表达的反式激活因子，在神经节中表达的潜伏感染的非洲绿色猴（AGM）。 猴子这一发现与其他嗜神经性α疱疹病毒的病毒潜伏期一致，但与VZV在潜伏感染的人神经节中表达几种病毒转录本和蛋白质（ORF 21，29，62和63最一致）的报道相反。

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. Varicella zoster virus (VZV) causes varicella (chickenpox), a common disease of childhood. Following resolution of the primary disease, the virus establishes latent infection in neural ganglia and may reactivate later in life, particularly in the elderly, to cause herpes zoster (shingles) and post herpetic neuralgia. VZV infections cause significant morbidity, especially in children, the elderly, and immunosuppressed patients. The VZV Oka vaccine currently in use is safe and effective for immunization of healthy children and susceptible adults. However, this vaccine is generally not recommended for some patients, including those immunocompromised individuals. The vaccine establishes a latent infection in the ganglia of the host and may reactive to cause herpes zoster. Studies to assess these shortfalls are limited due to the need for suitable animal models. A simian model of varicella disease has been developed using the simian counterpart virus, simian varicella virus, SVV, which infects and produces acute infection in nonhuman primates with clinical, pathological, immunological, and virological features similar to VZV infection of humans. A vaccine study was conducted and demonstrated that subcutaneous vaccination with VZV in nonhuman primates showed no replication when inoculated subcutaneously and offered no cross reactive protection against SVV, whereas similar subcutaneous vaccination with SVV showed cellular and humoral responses. Following latency, SVV expression was shown to be limited. A latency associated transcript (LAT) that overlaps and is antisense to the SVV gene 61 (HSV-1 ICP0 homolog), a transactivator of SVV gene expression, was expressed in neural ganglia of latently infected African green monkeys (AGM). monkeys. This finding is consistent with viral latency of other neurotropic alphaherpesviruses, but is in contrast to reports that VZV expresses several viral transcripts and proteins (ORFs 21, 29, 62, and 63 most consistently) in latently infected human ganglia.