The goals of our research are to further define immunity mechanisms, particularly T cell mediated immunity against herpes simplex virus (HSV) and how best to stimulate protective immunity with purified glycoprotein (gp) antigens. Mice will be immunized with HSV and at various times post infection their spleens or lymph node cells will be taken and stimulated in vitro with various antigen preparations to generate cytotoxic T lymphocytes (CTL) and to enumerate CTL precursors and helper T cell precursors by Poisson statistical analysis of limiting dilution assays. Liposomes containing defined HSV gp and appropriate H-2 antigens will be used to investigate the role of different gp at inducing CTL and other T cell responses in vitro. Glycoprotein containing liposomes will also be used to introduce gp into target cells to ascertain which gp act as target antigens for CTL. Experiments are planned in vivo to test the efficacy of glycoprotein subunit vaccines incorporated into liposomes along with appropriate adjuvants (such as muramyl dipeptide) at inducing CTL responses. The role of CTL of different HSV antigen specificities, T cell hybridomas and helper T cells in recovery from primary and recrudescent infection in model systems will also be investigated. Finally in vitro approaches will be used to determine how anti HSV CTL responses are regulated, in particular the role of suppressor cells and factors in the induction process. The results of our research should help in the development and evaluation of DNA free subunit glycoprotein vaccines for use against different diseases caused by HSV.
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