Protective immunity conferred by cytotoxic T lymphocytes directed against an immunodominant, MHC class I-restricted epitope of herpes simplex virus type 1 and 2

A vaccine for prevention of herpes simplex virus type 1/2 (HSV) infection does not exist, and the understanding of the immune response against HSV remains unclear. Therefore, this study has attempted to further the knowledge of the cell-mediated immune response to HSV infection by evaluating the ability of CD8+ cytotoxic T lymphocytes (CTL) to confer immunity to HSV. Recombinant vaccinia or influenza viruses were utilized to induce epitope-specific CTL responses directed against an immunodominant CTL recognition epitope of HSV glycoprotein B (gB498-505; amino acids SSIEFARL). These memory CTL directed against a single MHC class I-restricted epitope were demonstrated to confer protective immunity in a murine model of lethal HSV-2 encephalitis and reduce viral colonization of the central nervous system (CNS). The protection afforded by immunization with the recombinant vaccinia viruses expressing gB498-505 was found to be route-dependent. Mice administered intranasal or intraperitoneal immunizations were protected, while intravenous immunization failed to induce resistance to HSV-2 encephalitis. These studies were confirmed and extended utilizing a transgenic mouse strain, Line 359, which encode gB498-505. Results have indicated that Line 359 mice are tolerant to this HSV CTL epitope upon immunization with HSV or other gB498-505-expressing vectors. To determine whether the protection elicited by recombinant vectors is dependent upon induction of gB498-505-specific CTL or if other immune components confer resistance, Line 359 mice were utilized in protection studies. Immunization of Line 359 mice with vectors containing only gB498-505 failed to provide protection, but vectors containing full-length HSV gB were protective. The protection afforded by vectors expressing gB498-505 was thus dependent upon the induction of CTL, while immunization with full-length gB induced alternative protective immune responses in the absence of gB498-505-specific CTL. Additional studies indicated that tolerance to gB498-505 in Line 359 mice resulted in the detection of sub-dominant CTL against HSV. This study has indicated that the induction of HSV-specific CTL directed against a single epitope is sufficient for conferring resistance from HSV infection. The above findings support the role of CTL in the control of HSV infection of the CNS and suggest the potential importance of eliciting HSV-specific CTL in future vaccine design.