Immune Responses to Herpes Simplex Virus in Guinea Pigs (Footpad Model) and Mice Immunized with Vaccinia Virus Recombinants Containing Herpes Simplex Virus Glycoprotein D

Abstract

Vaccinia virus recombinants containing the herpes simplex virus (HSV) gene for glycoprotein D type 1 (gD-1) under control of an early (VP176) or late (VP254) vaccinia virus promoter or for HSV glycoprotein type 2 (gD-2) under control of the early promoter (VP221) were studied for their ability to induce protective immunity to HSV-2 in the guinea pig model of cutaneous recurrent disease and the mouse model of fatal disease. Titers of HSV-specific neutralizing antibody were similar in the two groups of immunized animals, but HSV-specific T cell responses were significantly higher in VP176-immunized than in VP254-immunized animals, as determined by lymphoproliferation (P < .005) and delayed-type hypersensitivity (P < .01) responses. The reduced responses correlated with poor expression of the gD protein and its impaired processing in infected antigen-presenting cells (splenic adherent and epidermal cells). VP176 immunization protected against primary (P << .001) and recurrent (P << .001) cutaneous HSV-2 lesions and ganglionic latency (62% protection) in the guinea pig and against zosteriform skin lesions and fatal disease in the mouse. Immunization with VP254 was not protective. In guinea pigs VP221 did not protect against primary HSV-2 cutaneous disease but did reduce the proportion of animals with recurrent disease (P < .05). This partial protection appears to be associated with the role of type-specific antigenic determinants in gD-2 immunoregulation.