This is a project that focuses on the development of a dental caries vaccine in humans, based on secretory IgA immune responses to glucosyltransferase from Streptococcus mutans using discrete, but integrated strategies. Project (I) will investigate the nature of T cell defects in resulting secretory IgA responses and will provide means for overcoming these defects. Studies will concentrate on GTF as a thymus dependent antigen of particular importance in dental caries. Methodology using isolated T cells and cloned antigen specific T cells will be used to study the best method(s) to reconstitute SIgA responses. The origin and nature of regulatory T cells required for IgA immune response to GTF will be studied. The subsets of these cells will be characterized as will the presence or absence of Fc alpha receptors using flow fluorocytometry. The GTF specific T cell involved in protective IgA response will be selected by panning, cloned and adoptively transferred into congenitally athymic recipients to test effects on dental caries. The goal of Project (II) is to develop an effective GTF dental caries vaccine. The labial minor salivary glands (MG) will be the source of immunization. Various doses of GTF will be topically applied to MG and the salivary IgA immune response will be tested. The existence and duration of an anamnestic response will be examined. The use of adjuvant to particularize GTF will also be tested as opposed to the immune response to soluble GTF. Further studies will utilize combined oral and topical routes of immunization to optimize immune response to GTF. The effect of this antibody on indigenous S. mutans will be assessed. The integration of these projects will provide an understanding of the regulatory mechanisms of secretory immunity and should allow a knowledgeable manipulation of the human host response to the important antigenic epitopes of GTF, so as to interfere with infection and disease caused by this oral pathogenic microorganism.
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