Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection

Abstract

Monoclonal antibodies specific for the five major glycoproteins of herpes simplex virus type 1 (HSV-1) were tested for their capacity to mediate immunity to ocular HSV-1 infection. The specificity of the immunoglobulin made by each monoclone was determined by immunoprecipitation of [14C]glucosamine-labeled polypeptides from detergent-solubilized HSV-1-infected cells. Of the five monoclonal antibodies studied, two immunoprecipitated glycoproteins gA/B, one immunoprecipitated glycoprotein gC, one immunoprecipitated glycoprotein gD, and one immunoprecipitated glycoprotein gE. All five were effective in passively transferring immunity to mice when they were given 4 to 24 h after HSV-1 infection on an abraded cornea. Four of the monoclonal antibodies were also evaluated for their capacity to neutralize HSV-1 and to promote complement-mediated cell lysis and antibody-dependent cellular cytotoxicity. It was found that none of these in vitro assays correlated with the protective activity of the antibodies in vivo. In fact, one of the monoclonal antibodies was unreactive in all three immunological reactions, even though it was highly effective in promoting recovery from HSV-1 induced ocular disease in vivo. The results suggest that antibodies can interact in vivo with virus-specific glycoproteins gA/B, gC, gD, and gE to initiate recovery from HSV-1-induced ocular disease, and that the therapeutic effectiveness of a specific monoclonal antibody does not correlate with its immunological reactivity in vitro.