IMMUNIZATION WITH A SINGLE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTE RECOGNITION EPITOPE OF HERPES-SIMPLEXVIRUS TYPE-2 CONFERS PROTECTIVE IMMUNITY

We have evaluated the potential of conferring protective immunity to h erpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-spec ific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a s ingle major histocompatibility complex class I-restricted CTL recognit ion epitope. We generated a recombinant vaccinia virus (rVV-ES-gB498-5 05) which expresses the H-2K(b)-restricted, HSV-1/2-cross-reactive CTL recognition epitope, HSV glycoprotein B residues 498 to 505 (SSIEFARL ) (gB498-505), fused to the adenovirus type 5 E3/19K endoplasmic retic ulum insertion sequence (ES). Mucosal immunization of C57BL/6 mice wit h this recombinant vaccinia virus induced both a primary CTL response in the draining lymph nodes and a splenic memory CTL response directed against HSV gB498-505. To determine the ability of the gB498-505-spec ific memory CTL response to provide protection from HSV infection, imm unized mice were challenged with a lethal dose of HSV-2 strain 186 by the intranasal (i.n.) route. Development of the gB498-505-specific CTL response conferred resistance in 60 to 75% of mice challenged with a lethal dose of HSV-2 and significantly reduced the levels of infectiou s virus in the brains and trigeminal ganglia of challenged mice. Final ly, i.n. immunization of C57BL/6 mice with either a recombinant influe nza virus or a recombinant vaccinia virus expressing HSV gB498-505 wit hout the ES was also demonstrated to induce an HSV-specific CTL respon se and provide protection from HSV infection. This finding confirms th at the induction of an HSV-specific CTL response directed against a si ngle epitope is sufficient for conferring protective immunity to HSV. Our findings support the role of CD8(+) T cells in the control of HSV infection of the central nervous system and suggest the potential impo rtance of eliciting HSV-specific mucosal CD8(+) CTL in HSV vaccine des ign.