Vaccinia recombinants as probes of relevant HSV-2-specific immunity

Abstract

Vaccinia recombinants expressing the glycoprotein D (gD) of HSV-1 (VP176) or HSV-2 (VP221) under control of an early vaccinia virus promoter or of HSV-1 under the control of a late promoter (VP254) were studied as probes for relevant immunity. The recombinants expressed comparable amounts of gD and grew equally well in vitro and in vivo VP176 immunization protected guinea pigs against primary (p {dollar}<{dollar} 0.005) and recurrent (p {dollar}<{dollar} 0.005) cutaneous HSV-2 disease, VP221 protected against recurrent disease and VP254 immunization afforded no protection. All vaccines protected mice at 10 days post infection, but VP176 gave superior protection on day 50 post immunization (p {dollar}<{dollar} 0.0001). Although neutralizing anti-HSV antibody and immunity to vaccinia antigens induced were identical, immunization with VP176 as compared to VP254 induced significantly higher levels of T-cell mediated immunity to HSV antigen as defined by lymphocyte transformation or delayed type hypersensitivity (P {dollar}<{dollar} 0.01). L3T4+ LNC from VP176 immunized animals mediated these effects and could transfer protection but required a second non-HSV immune, radiosensitive cell. Immunity induced by prior HSV-2 immunization was less effective than that induced by VP176 in terms of preventing primary disease (p {dollar}<{dollar} 0.01) and local viral replication (100 fold higher virus titers). This was associated with lower HSV-specific blastogenic and DTH response in HSV but not VP176 immune animals following HSV reexposure. VP254 but not VP176 infected antigen presenting cells failed to produce fully glycosylated gD. This defect correlated with the failure of VP254 infected epidermal or spleen cells to express gD on the cell surface or to present antigen.