Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection

Cytotoxic T cells are important in controlling herpes simplex virus type 2 (HSV-2) reactivation and peripheral lesion resolution. Humans latently infected with HSV-2 have cytotoxic T cells directed against epitopes present in tegument proteins. Studies in mice of immunity to HSV have commonly focused on immunodominant responses in HSV envelope glycoproteins. These antigens have not proved to be an effective prophylactic vaccine target for most of the human population. The murine immune response against HSV tegument proteins has not been explored. We analysed cellular responses in BALB/c mice directed against the tegument proteins encoded by UL46, UL47 and UL49 and against the envelope glycoprotein gD after DNA vaccination or HSV-2 infection. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 10⁶ responder cells. Peptide truncation studies, responder cell fractionation and major histocompatibility complex binding studies identified several CD8⁺ and CD4⁺ epitopes. Cellular responses to tegument protein epitopes were also detected after HSV-2 infection. Tegument proteins are rational candidates for further HSV-2 vaccine research.