CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

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A principal long-term goal of the research conducted under DE-06153 is to develop a dental caries vaccine that mediates protection via the mucosal immune system. Corollary long-term objectives necessary to achieve this goal are (a) determine the age at which mucosal immune mechanisms are sufficiently mature to manifest potentially protective immune responses, (b) to identify mutants streptococcal components that are sufficiently immunogenic to elicit potentially protective immune responses prior to colonization with a cariogenic flora, and (c) to evaluate the capacity of immune elements within minor salivary gland tissue to function as inductive sites for potentially caries-protective antibody formation within the oral cavity. Although these long-term objectives are targeted for caries immunity, the resulting research should permit enhancement of secretory immunity for many infectious diseases that invade via mucosal routes. The research described in this application is intended first to reveal the capacity for secretory immunity at an age that is correlated with initial streptococcal infection. Secondly, the antigenic relationships and potential for protective immunity of two novel mutants streptococcal components (GBP Antigen) that are immunogenic at the time of initial mutants streptococcal infection will be identified. Thirdly, the ability of different minor salivary gland compartments to manifest secretory immune response after local induction with alum-associated and microencapsulated tetanus toxoid will be measured. These objectives will be explored by pursuing the following specific aims: (1) analysis of secretory immune responses of young children to components of proteins (tetanus toxoid), polysaccharide conjugate (capsular polysaccharide of Haemophilus influenza b), cellular (Bordetella pertussis), or intact attenuated viral vaccines (poliovirus) administered immediately prior to the critical period of mutans streptococcal infectivity; (2) determination of the ability of Streptococcus mutans 59 kDa glucan binding protein (GBP) to elicit immune responses that interfere with the colonization and cariogenicity of mutans streptococci in a rat model of dental caries; (3) purification, evaluation of epitopic distinctiveness, and potential for induction of protective immune responses by mutans streptococcal Antigen (the component to which the most frequent salivary immune responses are detected during the initial period of MS infectivity); and (4) analysis of topical immunization of minor salivary glands with respect to distribution of salivary responses within different minor gland microenvironments (lower, upper labial and palatine) with alum-associated and microencapsulated tetanus toxoid, used as an analogue of a protein- based dental caries vaccine.