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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE005739-02
Application #
6350576
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Lipton, James A
Project Start
2001-02-01
Project End
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
2
Fiscal Year
2001
Total Cost
$47,348
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Gibson 3rd, Frank C; Savelli, Juan; Van Dyke, Thomas E et al. (2005) Gingipain-specific IgG in the sera of patients with periodontal disease is necessary for opsonophagocytosis of Porphyromonas gingivalis. J Periodontol 76:1629-36
Gibson 3rd, Frank C; Hong, Charlie; Chou, Hsin-Hua et al. (2004) Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 109:2801-6
Gyurko, Robert; Boustany, Gabriel; Huang, Paul L et al. (2003) Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis. Infect Immun 71:4917-24
Gonzalez, Dario; Tzianabos, Arthur O; Genco, Caroline A et al. (2003) Immunization with Porphyromonas gingivalis capsular polysaccharide prevents P. gingivalis-elicited oral bone loss in a murine model. Infect Immun 71:2283-7