ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

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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.