Varicella (chicken pox) is caused by infection with varicella-zoster virus (VZV). Primary infection with VZV is associated with severe infection in immunocompromised children. Varicella has been considered a benign illness in otherwise healthy children. However, with effective vaccines for other childhood viral infections varicella has emerged as a significant cause of serious illness in the general population. Research concerning VZV has been difficult because of the cell-associated nature of VZV replication in vitro and the lack of animal models for the investigation of VZV pathogenesis. The purpose of this study is to evaluate the strain 2 guinea pig as a model of acute primary VZV infection and of the immune response to primary VZV infection. The guinea pig is uniquely susceptible to infection with human VZV. A viremic phase following inoculation with VZV has been demonstrated in the strain 2 guinea pig. The occurrence of viremia suggests that the guinea pig model can be exploited as an analogue of primary human varicella since viremia appears to be fundamental to the pathogenesis of the initial infection with VZV in the human host. The investigation of the guinea pig as a model of VZV immunity is important given recent efforts to prepare a VZV vaccine. This study will investigate immunity to VZV in the strain 2 guinea pig after inoculation with infectious VZV for comparison with immunity to the virus that can be elicited by immunization with VZV proteins. VZV proteins antigens will be prepared by immunoaffinity using murine monoclonal antibodies to specific VZV proteins. Humoral immunity will be measured by solid phase radioimmunoassay for VZV IgG and IgM antibodies, by VZV neutralization assay and by immune transfer (Western blot). Cellular immunity will be assessed by in vitro T-lymphocite proliferation of peripheral blood mononuclear cells stimulated with VZV antigen. Methods to optimize the detection of viremia will be investigated to facilitate the use of the model to evaluate approaches for restricting VZV replication in vivo. Viral culture of peripheral blood mononuclear cells will be done in parallel with an immunofluorescence method which uses monoclonal antibody to detect VZV antigens on these cells. In situ hybridization with radiolabeled cloned fragments of VZV DNA will be evaluated for the identification of the virus in peripheral blood cells. Protection against viremia will be used as an in vivo biologic measure of the efficacy of immunization with VZV proteins antigens, passive antibody to VZV and antiviral drugs.
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