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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
Administrative Core[Biometry Core][Biomedical Core][Biobehavioral Core]
[Dr. Rutger Persson]
[ Dr. Murray R. Robinovitch][ Dr. Samuel F. Dworkin]
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