Immunity against cutaneous herpes simplex virus infection: Host defense mechanisms mediated by IFN-gamma and active protection induced by DNA vaccination

The goal of this dissertation is to understand the immune responses generated against cutaneous herpes simplex virus (HSV) infection, with an emphasis on the role of gamma-interferon (IFN-;A T-cell mediated inflammatory response dominated by IFN-;To test the principle that genetically engineered epitopes in a plasmid DNA can efficiently induce specific immunity, a study on HSV-specific immune responses induced by vaccinating mice with a plasmid DNA (pcMini) encoding cytotoxic T lymphocyte (CTL), helper T and B cell epitopes from HSV is described in this dissertation. Following immunizations with pcMini, mice developed epitope-specific CTLs comparable to the responses induced by live HSV. Antibody, lymphoproliferative responses, and T cell cytokine release were also detected. The protection provided by minigene vaccination was significant; however, not as efficient as live virus immunization. The DNA minigene approach may prove useful to define and induce immune responses against minimal antigenic determinants.;To address the question of whether immune responses to a vector-encoded antigen can be enhanced by the activation of antigen-presenting cells in the local environment, the effects of co-inoculation of an HSV glycoprotein (gB)-expressing plasmid with a plasmid encoding mouse granulocyte-macrophage colony-stimulatory factor (GM-CSF) on modulation of gB-specific immune responses are evaluated in this dissertation. The results show that co-administration of GM-CSF DNA provided increased resistance to HSV infection and this protective response could be related to the enhanced immune induction of CD4+ T cells and B cells responses.