Since delivery of antigens to the gut-associated lymphoid tissue (GALT or Peyer's patches) results in a generalized mucosal immune response and since avirulent derivatives of invasive Salmonella strains are able to attach to, invade and persist in the GALT, we will continue our endeavors to construct and evaluate recombinant avirulent Salmonella expression colonization and/or virulence antigens specified by genes cloned from other pathogens for their ability to induce secretory, humoral and cellular immune responses. Our immediate objectives will be to make use of cloned genes from the Streptococcus mutans group of microorganisms which constitute the principal etiologic agent of dental caries and where a secretory immune response is known to be the most effective means to confer protective immunity. More specifically, we will: (1) construct vectors that permit recombinant clones to be stably maintained in avirulent Salmonella following colonization in the murine host and develop methods to insert S. mutans genes into the chromosome of avirulent Salmonella strains, (2) construct avirulent Salmonella expressing surface protein antigen A (SpaA) epitopes in the cytoplasm and/or on the cell surface, (3) construct avirulent Salmonella strains expresseing dextranase epitopes in the cytoplasm and/or on the cell surface, (4) evaluate the ability of recombinat avirulent Salmonella strains to immunize mice and to quantitate the immune response in regard to antibody production, inhibition of S. mutans colonization on teeth and protective immunity ot S. mutans-induced dental caries, and (5) use the systems developed to examine the basic attributes of the mucosal immune system, including studies of the influence of animal age, nature of and means of inducing suppression (oral tolerance), the duration and location of memory, and the best means for inducing secondary immune responses. In the future, it is our expectation to use the knowledge gained from these studies in collaboration with others to evaluate immunity to periodontal disease caused by Bacterioides gingivalis, Hemophilus (Actinobacillus) actinomycetemcomitans and Actinomyces viscosus.
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