Periodontitis is a major cause of tooth loss in adults in the US and worldwide. There is a compelling need for new approaches to prevention and control. Use of a vaccine may be possible since the disease is caused by a small group of gram-negative bacteria among which Porphyromonas gingivalis predominates. Vaccine development is hampered by a gap in our fundamental knowledge about the role of immune responses in modulating periodontal tissue destruction. Studies in animal models are necessary to obtain the needed information. The Principal Investigator has shown that immunization of the nonhuman primate Macaca fascicularis, using a killed P. gingivalis vaccine, suppresses or blocks periodontal destruction as assessed by alveolar bone loss. The mechanisms may involve antibody-mediated reduction in levels of PGE2 and other inflammatory mediators, and immune neutralization of P. gingivalis virulence factors as well as opsonization. Immunization studies are likely to continue to close the gaps in our understanding of the pathogenesis. The Principal Investigator and others have demonstrated that a vaccine containing cysteine protease from P. gingivalis has high potential for inducing protection. The Principal Investigator in a pilot study has demonstrated that immunization of M. fascicularis with a vaccine containing porphypain-2 was more effective that the whole cell vaccine in reducing bone loss. PGE2 levels in crevicular fluid were significantly reduced. The Principal Investigator proposes to confirm and extend these observations by studying 10 animals immunized with gingipains and 10 control animals using their well-established protocol. The primary outcome measure will be radiographic assessment of alveolar bone status. Titers and functional biologic properties of serum, salivary, and GCF antibodies will be measured, and P. gingivalis and five other bacteria in the flora monitored by DNA probes. Effects of immunization on levels of PGE2, IL-1beta, and TNF-alpha in GCF will be determined and antibody mediated modulation of P. gingivalis virulence factors assessed. Gingival biopsies will be taken to evaluate the effect of immunization on the cellular infiltrate by immunocytochemistry and inflammatory mediator expression by in situ hybridization. Additional safety data will be obtained by necropsy of some of the animals at the end of the study. These observations will contribute in a major way to closing the gaps in our knowledge of the role of the host immune response in the pathogenesis of periodontitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE012939-01A1
Application #
2903517
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1999-09-20
Project End
2002-07-31
Budget Start
1999-09-20
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Dentistry
Type
Schools of Dentistry
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Page, R C; Lantz, M S; Darveau, R et al. (2007) Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis. Oral Microbiol Immunol 22:162-8
Pawlowski, Adrian P; Chen, Allen; Hacker, Beth M et al. (2005) Clinical effects of scaling and root planing on untreated teeth. J Clin Periodontol 32:21-8
Roberts, Frank A; Houston, Laura S; Lukehart, Sheila A et al. (2004) Periodontitis vaccine decreases local prostaglandin E2 levels in a primate model. Infect Immun 72:1166-8
Page, R C (2001) Periodontitis and respiratory diseases: discussion, conclusions, and recommendations. Ann Periodontol 6:87-90
Page, R C (2000) Vaccination and periodontitis: myth or reality. J Int Acad Periodontol 2:31-43