title: Cell-mediated immunologic responses and recurrent genital herpes in the guinea pig. Effects of glycoprotein immunotherapy.
abstract: 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.
authors.affiliation: J. N. Gamble Institute of Medical Research, Children's Hospital Research Foundation, Cincinnati, OH 45219.
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: L J
authors.initials: LJ
authors.lastname: Jenski
authors.forename: M G
authors.initials: MG
authors.lastname: Myers
authors.forename: L R
authors.initials: LR
authors.lastname: Stanberry
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology* / Q000628:therapy; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D012008:Recurrence; D018139:Simplexvirus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines
chemical_list: D007376:Interleukin-2; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1