GENETIC VACCINES AND IMMUNITY TO HERPES SIMPLEX VIRUS

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Effective vaccines are not currently available for many agents including herpes simplex virus (HSV). For optimal defense against HSV it may be necessary to maximize CD8+ T cell and CD4+ T cell responses of the Th1 subtype, since these components of immunity are crucial for prompt and effective viral clearance. Inducing such responses could be achieved by appropriately designed DNA (genetic) vaccines administered by routes which maximally engage cells of the dendritic cell series. Initially using in vitro systems, DNA constructs encoding either full length proteins of HSV or minigenes encoding known T and B cell epitopes will be tested for their ability to induce various types of immune responses induced. The influence of the costimulatory cytokine environment will also be evaluated as regards the CD4+ Th1 or Th2 nature of the response induced. Subsequently, constructions found to act as effective immunogens in vitro will be used to immunize mice in various ways. Delivery systems will include transfected dendritic cells, liposomes, as well as microparticles encoated with DNA and administered via a gene gun. Immunizations responses will be evaluated both in terms of the type and magnitude of immune responses generated as well as for their effectiveness at conferring protection in mouse models of HSV infection. The findings should be relevant to the future development of vaccines that will successfully control HSV infections.