Effects of in vivo depletion of immunocyte populations on herpes simplex virus glycoprotein D vaccine-induced resistance to HSV2 challenge.
BALB/c mice, preimmunized with a protective dose of native herpes simplex virus type 1 glycoprotein D (ngD1) vaccine, were depleted of selected immunocyte populations in vivo using monoclonal antibodies directed at Thy1+, L3T4+, or Lyt2+ cells. Following immunization and depletion, animals were inoculated with varied challenge levels of herpes simplex virus type 2 (HSV2) in the footpad and were monitored for disease. Both depleted undepleted gD-immunized mice were significantly protected when compared with placebo controls. T-cell-independent protection in Thy1 and L3T4-depleted ngD1-immunized animals was effective at low and moderate levels of HSV2 challenge levels, high levels of HSV2 giving high symptom scores in immunized and depleted mice. Depletion of Lyt2+ cells had no significant effect on the outcome of HSV2 infection. Depleted and nondepleted animals also were assessed in parallel for cellular and humoral responsiveness to ngD1 and to HSV antigens in vitro. Lymphoproliferative responses were abrogated in gD-immunized mice treated with anti-Thy1 or anti-L3T4, anti-Lyt2 treatment having little effect. Postimmunization T-cell depletion did not undermine ELISA or neutralizing antibody responses. These findings suggest that at low to moderate levels of virus challenge vaccine-elicited antibody plays a primary role in limiting the severity of infection, T-cell-mediated protective responses being of enhanced significance only at high levels of virus challenge.
Mishkin
E M
EM
Department of Viral Vaccine Research and Development, Lederle-Praxis Biologicals, Pearl River, New York.
Blasiak
M
M
Giorgio
D
D
Ishizaka
S T
ST
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D022283:Herpesvirus Vaccines; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D014765:Viral Vaccines; C069093:herpes simplex virus-1 glycoprotein D vaccine