Research Project
6176118
Mutans streptococci are the principal microorganisms associated with dental caries in humans. Mutans streptococci (MS) colonize and begin to accumulate on the tooth surfaces of most children between the ages of approximately 18 and 36 months of age. A critical component in the accumulation of cariogenic streptococci is the formation of glucan, which is synthesized by the catalytic action of MS glucosyltransferases (GTF) on sucrose. Glucan increases the pathogenic potential of mutans streptococci by providing binding sites for cariogenic mutans streptococci as well as changing the porosity of dental plaque. GTF from MS can induce an immune response that inhibits GTF catalytic activity, protect rodents from dental caries, and interfere with the reaccumulation of indigenous MS in humans. Although uncertain, it is likely that protection involves inhibition of the catalytic and/or glucan binding activities of GTF. Our approach to the development of childhood vaccine for dental caries is to prepare microparticles of the bioerodible poly(d,l-lactide-co-glycolide) (PLGA), including therein both GTF and gelatin as a bioadhesive, for nasal administration. Adhesion to the nasal mucosa increases the transit time of the microparticles and facilitates absorption of these GTF-containing microparticles, thereby increasing the potential for uptake of microparticles to inductive immune tissue. We have demonstrated that these microparticles produce elevated salivary IgA and serum IgG in response to nasal administration to rates significantly greater than observed for unincorporated GTF. The Phase II strategy is directed to opitmizing the PLGA/GTF/gelatin system developed in Phase I and demonstrating protection against dental caries in a challenge test using the rat model. PROPOSED COMMERCIAL APPLICATION Childhood immunization by oral or nasal delivery are the favored routes because they are simple, rapid and reduce the trauma to the child occasioned by injection. The commercial potential of an enhanced delivery system for mucosal immunization is enormous: universal childhood immunization could virtually eliminate tooth decay and its associated problems in childhood. Further, the development of a more efficient delivery system for mucosal induction of immunity would find broad application to mucosal infections other than dental caries.
