Periodontitis is a chronic disease of high prevalence in the United States and other countries. Successful treatment requires trained specialists and it is costly, sometimes painful, and not readily available to much of the population. There is a compelling need for new approaches to prevention and control. Recent developments support the idea that a vaccine may be feasible, especially in highly susceptible groups and individuals. Periodontitis is infectious, and identity of several specie of participating bacteria is known. Most patients mount a humoral immune response to antigens of the infecting pathogens. We do not know which antigens are involved, nor have we an understanding of the functional characteristics of the antibodies produced. Most importantly, we do not know if the antibodies are protective, destructive, or irrelevant to the course of the disease. This multidisciplinary program project proposes to resolve some of these fundamental issues. It consists of four separate but highly interrelated projects, and a core program that serves all projects. using ELISA tests, immunoblots, antibody- positive patient sera. and various fractions from relevant bacteria, we will identify and characterize the major antigens humans recognize. We will measure the quantity and biological activity of antibodies present in sera of patients and periodontally normal individuals. To determine whether serum antibodies are protective, destructive, or irrelevant to progression of periodontitis, we will induce humoral immunity in Macaca fascicularis, using a vaccine containing a newly developed adjuvant plus, killed B. gingivalis, and subsequently induce periodontitis in immunized and nonimmunized animals. We will monitor levels and properties of serum antibodies, and composition of the subgingival microflora. Presence and progress of the disease will be assessed by measurement of inflammation, attachment level, and alveolar bone loss. Successful completion of the studies will reveal which antigens are important, the functional characteristics of observed serum antibodies, the effect of immunization on composition of the subgingival microflora, and on initiation and progress of ligature-induced periodontitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
5P01DE008555-03
Application #
3095022
Study Section
Special Emphasis Panel (SSS (G))
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Dentistry
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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
Yang, E Y; Tanner, A C R; Milgrom, P et al. (2002) Periodontal pathogen detection in gingiva/tooth and tongue flora samples from 18- to 48-month-old children and periodontal status of their mothers. Oral Microbiol Immunol 17:55-9
Tanner, A C R; Milgrom, P M; Kent Jr, R et al. (2002) The microbiota of young children from tooth and tongue samples. J Dent Res 81:53-7
Tanner, A C R; Milgrom, P M; Kent Jr, R et al. (2002) Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study. Oral Microbiol Immunol 17:379-87
Fan, Q; Sims, T; Sojar, H et al. (2001) Fimbriae of Porphyromonas gingivalis induce opsonic antibodies that significantly enhance phagocytosis and killing by human polymorphonuclear leukocytes. Oral Microbiol Immunol 16:144-52
Nakagawa, T; Sims, T; Fan, Q et al. (2001) Functional characteristics of antibodies induced by Arg-gingipain (HRgpA) and Lys-gingipain (Kgp) from Porphyromonas gingivalis. Oral Microbiol Immunol 16:202-11
Sims, T J; Schifferle, R E; Ali, R W et al. (2001) Immunoglobulin G response of periodontitis patients to Porphyromonas gingivalis capsular carbohydrate and lipopolysaccharide antigens. Oral Microbiol Immunol 16:193-201
Robinovitch, M R; Ashley, R L; Iversen, J M et al. (2001) Parotid salivary basic proline-rich proteins inhibit HIV-I infectivity. Oral Dis 7:86-93
Fan, Q; Sims, T J; Nakagawa, T et al. (2000) Antigenic cross-reactivity among Porphyromonas gingivalis serotypes. Oral Microbiol Immunol 15:158-65

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