Animal models to design & evaluate improved VZV vaccines

描述(申请人提供)：水痘带状疱疹病毒(VZV)引起水痘(水痘)，一种常见的儿童疾病。急性疾病解决后，VZV在神经节内建立潜伏感染。该病毒可能在晚年重新激活，导致带状疱疹(带状疱疹)和带状疱疹后神经痛。VZV感染会导致严重的发病率，特别是在儿童、老年人和免疫抑制患者中。VZV Oka疫苗对健康儿童和易感人群的免疫是安全有效的。然而，这种减毒活疫苗一般不推荐给一些患者，包括免疫功能低下的人。此外，疫苗会在宿主的神经节内建立潜伏感染，并可能重新激活以导致带状疱疹。由于需要合适的动物模型，评估VZV抗病毒疗法和疫苗的研究有限。这项提案的总体目标是开发用于评估改进的VZV疫苗的动物模型。具体目标是： *评估VZV Oka疫苗对非人类灵长类动物有效免疫的能力，以及在随后与猿猴水痘病毒攻击后预防水痘的能力。 *评估VZV疫苗病毒在免疫猴子的神经节中建立潜伏感染和表达潜伏相关转录本(LAT)的能力。 *研制表达猴免疫缺陷病毒(SLV)gp120和nef抗原的重组VZV疫苗，并评估VZV-SLVenv/nef重组疫苗免疫和保护猴子免受水痘和猴艾滋病的能力。 这些发现可能导致改进的VZV疫苗，有效地预防水痘，但不会建立潜伏感染或重新激活以导致带状疱疹和带状疱疹后神经痛。这项研究还可能为使用VZV疫苗作为重组载体来免疫其他传染病病原体，特别是人类免疫缺陷病毒(HIV)提供支持。

DESCRIPTION (provided by applicant): Varicella zoster virus (VZV) causes varicella (chickenpox), a common disease of childhood. Following resolution of the acute disease, VZV establishes latent infection in neural ganglia. The virus may reactivate later in life to cause herpes zoster (shingles) and postherpetic neuralgia. VZV infections cause significant morbidity, especially in children, the elderly, and immunosuppressed patients. The VZV Oka vaccine is safe and effective for immunization of healthy children and susceptible adults. However, this live attenuated vaccine is not generally recommended for some patients including immunocompromised individuals. In addition, the vaccine establishes latent infection in ganglia of the host and may reactivate to cause herpes zoster. Studies to assess VZV antiviral therapies and vaccines are limited due to the need for suitable animal models. The overall goal of this proposal is to develop animal models for evaluation of improved VZV vaccines. The specific aims are: * To evaluate the ability of the VZV Oka vaccine to effectively immunize nonhuman primates and to protect against varicella following subsequent challenge with simian varicella virus. * To evaluate the ability of the VZV vaccine virus to establish latent infection and express latency associated transcripts (LATs) in ganglia of immunized monkeys. * To develop a recombinant VZV vaccine that expresses the simian immunodeficiency virus (SlV) gp120 and nef antigens and to evaluate the ability of the VZV-SlVenv/nef recombinant vaccine to immunize and protect monkeys against varicella and simian AIDS. The findings may lead to improved VZV vaccines that effectively protect against varicella, but do not establish latent infection or reactivate to cause herpes zoster and postherpetic neuralgia. The study may also provide support for use of the VZV vaccine as a recombinant vector for immunization against other infectious agents, particularly human immunodeficiency virus (HIV).