This proposal proposes to reduce the incidence of herpes induced blindness through therapeutic vaccination. In the previous research period, the investigator has indicated therapeutic vaccine efficacy in terms of statistically significant that reduced recurrent HSV-1 ocular disease and HSV-1 shedding. The investigator has hypothesized that the therapeutic vaccine efficacy seen is due to local ocular/mucosal immune response rather than a systemic immune response. The investigator's group has produced four papers directly related to their work on therapeutic vaccination. All papers have been submitted at this time (none accepted).
The specific aims to be addressed in the present application are (1) to test the hypothesis that therapeutic vaccine efficacy and duration against recurrent ocular HSV-1 can be extended by periocular booster inoculations with a subunit vaccine, or with HSV-1 DNA ocular vaccines or live HSV-1 ocular vaccines; (2) to test the hypothesis that therapeutic vaccine efficacy against recurrent ocular HSV-1 is due to common mucosal immunity rather than just local ocular mucosal immunity; and (3) to verify the hypothesis that sIgA is the specific mucosal immune response most important for therapeutic vaccine efficacy against recurrent ocular HSV-1.
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