title: 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.
authors.affiliation: Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: L
authors.initials: L
authors.lastname: Aurelian
authors.forename: C C
authors.initials: CC
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Wachsman
authors.forename: E
authors.initials: E
authors.lastname: Paoletti
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D006168:Guinea Pigs; D022283:Herpesvirus Vaccines; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D012008:Recurrence; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; C069093:herpes simplex virus-1 glycoprotein D vaccine