Animal models to design & evaluate improved VZV vaccines

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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).