Immunomodulation of Bone Destruction with a Novel Porphyromonas Gingivalis Protein

Objective: In previous studies we showed that biasing the immune response against an antigen extract of Porphyromonas gingivalis (Pg) to the Th1 phenotype dramatically increases inflammatory bone resorption following oral infection with Pg. In the present study we evaluated the ability of a single cloned Pg protein, encoded by PG_1841, for its immunomodulatory effects on bone loss following immunization under Th1 and Th2 biasing conditions.

Methods: PG1841 was identified as an immunodominant Pg antigen by T cell expression cloning. Recombinant PG1841 was expressed and purified using standard methodologies. C57Bl/6 mice were infected with Pg W83 subcutaneously to determine if PG1841 is expressed and is immunogenic in vivo. To determine effects on inflammatory bone resorption, mice were pre-immunized with rPG1841 under Th1 (alum + CpG) or Th2 (alum alone) biasing conditions. Th biasing was confirmed by serum antibody responses to PG1841 (IgG1/IgG2a) and by lymphoid cell expression of IL-4/IFN&Gamma. Effects on inflammatory bone resorption were evaluated using a periapical lesion model. Bone loss was measured by micro-computed tomography.

Results: Subcutaneous infection of mice with Pg W83 induced a strong Th1 biased response to PG1841, as indicated by specific serum antibody (IgG2a > IgG1). Mice immunized with rPG1841 under Th1 and Th2 inducing regimens showed the expected systemic immune response biasing. rPG1841 immunized Th1-biased mice challenged with Pg into dental pulp tissue developed severe periapical bone loss. In contrast, rPG1841 Th2-biased mice had no exacerbation of resorption when compared to adjuvant immunized control animals.

Conclusion: We conclude that selected immunodominant antigens of Pg that normally induce a Th1 response may reduce inflammatory bone loss if presented in a Th2 biasing adjuvant formulation. This approach may be useful for the development of vaccines or immunotherapeutics to prevent inflammatory bone loss caused by Pg.

Supported by NIDCR grants DE-09018 and T32-DE-007327.