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 less than .005) and delayed-type hypersensitivity (P less than .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 much less than .001) and recurrent (P much less than .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 less than .05). This partial protection appears to be associated with the role of type-specific antigenic determinants in gD-2 immunoregulation.