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. 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.