Regulation of Expression of Herpes Simplex Virus (HSV) Glycoprotein D in Vaccinia Recombinants Affects Their Ability to Protect from Cutaneous HSV-2 Disease

The effect of regulation of herpes simplex virus (HSV) type 1 glycoprotein D (gD-1) gene expression on HSV-specific immune response and protection from cutaneous HSV-2 disease was studied using vaccinia virus recombinants containing gD-1 under the control of early (VP176) or late (VP254) vaccinia virus promoters. Expression of gD-1 in VP176 infected cells was first observed at 2 h after infection. It did not depend on viral DNA replication. In VP254-infected cells, gD-1 was first observed at 24 h after infection and its expression depended on DNA replication. Immunized guinea pigs had similar titers of HSV-specific neutralizing antibody. However, HSV-specific T cell responses were significantly higher in VP176- than in VP254-immunized animals as determined by lymphoproliferation (P < .005) and delayed type hypersensitivity (P < .01). The reduced T cell responses of VP254-immunized guinea pigs correlated with poor gD-1 expression in VP254-infected antigen presenting cells (splenic adherent and epidermal cells). Immunization with VP176, but not with VP254, protected guinea pigs from primary (P < .0005) and recurrent (P < .00(5) cutaneous HSV-2 lesions.