Cell-mediated immunologic responses and recurrent genital herpes in the guinea pig. Effects of glycoprotein immunotherapy

The specific immune alterations associated with HSV recurrences are ill defined although it appears that alterations in cell-mediated immune mechanisms are more likely associated with recurrent disease than humoral immunity. Immunization with HSV glycoproteins B and D (gBgD) after primary HSV infection has reportedly reduced the frequency of recurrences but the mechanisms remain unidentified. We therefore evaluated the effects of immunization with cloned gBgD on selected cell-mediated immune responses and their relationship to recurrent disease by using the guinea pig model of genital HSV-2 infection. In two experiments, immunization with gBgD + CFA on days 21 and 42 after HSV-2 inoculation significantly decreased the number of subsequent recurrent lesion days observed whereas CFA alone had no effect. Immunization with gBgD + CFA increased the lymphoproliferative and in vitro IL-2 response to gBgD more than to whole HSV-2 Ag preparations. Peak responses were observed 2 wk after the second immunization. The HSV-specific cytolytic response was also persistently increased beginning 1 wk after the first immunization. Analysis including both untreated and gBgD-immunized animals revealed that recurrent lesion days were inversely correlated to the IL-2 response to whole HSV-2 Ag (p less than 0.0001), the IL-2 response to gBgD (p = 0.0004), and the HSV-specific cytolytic response (p = 0.005 and 0.003 in two experiments, respectively). When the untreated group was analyzed separately, only the IL-2 response to whole HSV-2 Ag correlated to recurrences (p = 0.007). HSV glycoprotein immunization may increase IL-2 or other cytokines secreted by HSV-sensitized T cells increasing critical immune responses, such as NK- or lymphokine-activated killer-mediated cytolysis, that could eliminate the reactivated virus before the development of clinically apparent lesions.