ORAL IMMUNIZATION WITH GINGIPAIN DELIVERED BY SALMONELLA

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Porphyromonas gingivalis is an important pathogen in adult periodontal disease. Several studies have suggested that the cysteine-proteases (gingipains) produced by this organism play an important role during P. gingivalis-induced periodontal disease. Recently, several investigations indicate that immunization of mice with gingipains or regions of these gingipains provide protection from subsequent P. gingivalis challenge. As, P. gingivalis infection begins in the periodontal pocket, we believe that delivery of gingipains to mucosal surfaces represents a novel approach to attempt to prevent P. gingivalis-induced disease. Oral immunization with attenuated Salmonella typhimurium has been demonstrated to be an effective way to enhance the host immune response at mucosal surfaces. We propose to construct attenuated S. typhimurium strains expressing gingipain region-specific/LT-B (binding domain of E. coli heat-labile enterotoxin) fusions. The ability of oral immunization of these Salmonella strains to protect against P. gingivalis-mediated bone loss will be evaluated m a mouse-P. gingivalis oral infection model. These data will provide insight into the usefulness of mucosal immunization strategies to prevent P. gingivalis-induced disease and begin the process of characterizing which gingipain-specific epitopes mediate this protective host immune response.