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Dr. Roy Page DDS, PhD

Associate Dean,
Research Center in Oral Biology

Professor, Department of Pathology
Professor
, Department of Periodontics

Dr. Roy Page
The major objective of Dr. Page's present research effort is to develop a vaccine for use against gram-negative infections, using periodontitis, a commonly occurring gram-negative infectious disease affecting bone and connective tissue around teeth, as a model. There is evidence that a vaccine may not only be effective in prevention of these diseases but also as a form of treatment, especially in severe, refractory cases. The primary pathogens involved in causing periodontitis are Porphyromonas gingivalis and Bacteroides forsythus. Roughly half of young adults with severe periodontitis are seronegative for antigens of their infecting bacteria. Treatment consisting of removal of bacterial deposits from the roots of the teeth results in marked clinical improvement. Treatment induces a bacteremia and causes seronegative patients to seroconvert and to produce higher titers of biologically more effective serum antibody mostly of the IgG2 subclass.

Dr. Page's group has developed a primate model of periodontitis using Macaca fascicularis and demonstrated that immunization using a vaccine containing formalinized intact P. gingivalis bacteria inhibits and blocks progression of periodontitis. We are currently determining which antigenic components of P. gingivalis are responsible for the observed protection. We are focusing on cysteine protease and lipopolysaccharide (LPS). The immunized animals produced high titers of serum antibodies to both of these components. Cysteine protease is present in large quantities on the bacterial cell surface and it is a potent virulence factor accounting for hemagglutinin and adhesin as well as proteolytic activities. LPS is also a potent virulence factor as manifested by its role in toxic shock syndrome. Patients manifest serum antibodies not only to epitopes in the O-side chains but also in core carbohydrate and lipid A. LPS contains highly conserved antigenic epitopes that are shared among many gram-negative bacteria. Such epitopes may prove to be effective in inducing protection.

Dr. Page is also investigating mechanisms whereby serum antibodies prevent induction and progression of periodontitis. The induced antibodies are effective at opsonization and enhancing phagocytosis and killing of gram-negative bacteria. In addition, both immunized monkeys and humans contain blocking antibodies that may affect the early stages of the inflammatory response and production of mediators such as prostaglandin E2 which mediate alveolar bone destruction.

Recent publications

Persson GR, Engel D, Whitney C, Darveau R, Weinberg A, Brunsvold M, and Page RC. Immunization against Porphyromonas gingivalis inhibits progression of experimental periodontitis in nonhuman primates. Infect. Immun. 62:l026-l03l, 1994.

Darveau RP, Cunningham MD, Bailey T, Seachord C, Ratcliffe K, Bainbridge B, Dietsch M, Page RC, and Aruffo A. The ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion. Infect. Immun. 63:l3ll-l3l7, l995.

Vasel D, Sims T, Bainbridge, Weinberg A, Houston L, and Page RC. Shared antigens of Porphyromonas gingivalis and Bacteroides forsythus. Oral Microbiol. Immunol. In press l996.


Address:

Dr.Roy Page DDS, PhD
Associate Dean, Research Center in Oral Biology
University of Washington, Box 357480
Seattle, Washington 98195-7444
(206) 543-5599
fax: (206) 685-8024
e-mailroypage@u.washington.edu


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