Antibody-Mediated Protection against Genital Herpes Simplex Virus type 2 Disease in Mice by Fc gamma Receptor -Dependent and -Independent Mechanisms (41.8)

Abstract

Abstract The requirement for Ab -Fcγ receptor (FcγR) interactions or for virus neutralization in protection against genital HSV-2 challenge was examined. Serum IgG Ab isolated from HSV-immune mice protected normal mice against HSV-2 disease when administered prior to challenge. However, protection was significantly diminished in mice lacking the γ chain subunit utilized in FcγRI, FcγRIII, FcγRIV, and FcεRI and in normal mice depleted of FcγR+, Gr-1+ immune cells suggesting protection was largely mediated by an FcγR-dependent mechanism. To test if FcγR-independent antibody-mediated mechanisms might manifest protection differently, a highly neutralizing, HSV glycoprotein D -specific monoclonal antibody (mAb) was utilized. Administration of IgG1, IgG2a, or IgG2b switch variants of the mAb did not prevent infection of the genital tract but resulted in lower virus loads in the vaginal epithelium and provided significant protection against disease and acute infection of the sensory ganglia independently of host FcγR expression. Together, these data demonstrate two distinct antibody effector mechanisms capable of providing substantial protection against genital HSV-2 disease. The presence of either FcγR -dependent Ab or strongly neutralizing Ab did not completely prevent HSV-2 infection but limited initial infection of genital and neuronal tissues and diminished HSV-2 disease. NIH Grants AI42815 and AI054444.