Herpes simplex virus (HSV) is an important ocular pathogen in man. Following infection both cellular and humoral immune responses are elicited. However, the relative contribution that each makes toward limiting or exacerbating virus infection is poorly understood. We and other investigators have shown that passive transfer of HSV-specific monoclonal antibody (mcAb) will enable the host to resist a lethal challenge dose of virus. More recently, it has been found that mcAbs specific for HSV glycoproteins given 24 hours after corneal infection are able to prevent or ameloriate development of stromal disease and promote resolution of HSV eye infection. Using a murine ocular infection model, we propose to investigate basic aspects of how antibody can control HSV replication. McAbs specific for HSV glycoproteins, gD, and selected other glycoproteins, will be purified, characterized, and tested for their capacity to inhibit HSV replication and promote virus clearance from corneal tissue of the BALB/c mouse. In conducting this work, special emphasis will be placed on evaluating the importance of immunoglobulin isotype and epitope specificity. A primary goal is to investigate the mechanism(s) by which antibody can exert its protective effect. The hypothesis to be tested is that antibody-dependent cellular cytotoxicity is an important defense mechanism in vivo. The information gained from these studies will identify properties anti-HSV antibodies must have in order to protect optimally in vivo, and provide new insights into the role the humoral immune response plays in containing virus infection.
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