Protection from herpes simplex virus type 2 is associated with T cells involved in delayed type hypersensitivity that recognize glycosylation-related epitopes on glycoprotein D.

Immunization of mice with a vaccinia recombinant (VP176) that expresses a fully glycosylated herpes simplex virus (HSV) glycoprotein D (gD) induces long-term (greater than or equal to 50 days) HSV-specific lymphoproliferation and delayed type hypersensitivity (DTH) responses, the ability to eliminate a high challenge dose of HSV-2 from the epidermis and protection from fatal disease due to HSV replication in the nervous system. Adoptive transfer studies indicate that protection is mediated by the DTH functions of L3T4+ cells and requires the contribution of a non-specific irradiation-sensitive cell. Long-term protection (defined as that seen at greater than or equal to 50 days after immunization) from fatal HSV-2 challenge, virus clearance from the epidermis, and HSV-specific T-cell responses are not induced by a partially glycosylated gD expressed by a vaccinia recombinant (VP254) in which gD is controlled by a late vaccinia virus promoter. However, mice immunized with VP254 are protected from HSV-2 challenge early (day 10) after immunization. The VP254-induced protection is HSV-specific, but it is not mediated by L3T4+ and Lyt2+ cells. The findings are discussed within the context of future developments of anti-HSV vaccines.