CpG Oligodeoxynucleotides Adjuvant for Mucosal Immunity to Porphyromonas gingivalis

Objectives: This study has assessed the potential of a mucosal adjuvant, synthetic CpG oligodeoxynucleotides (CpG ODN) for the induction of mucosal immunity against 40-kDa outer membrane protein (40k-OMP) of Porphyromonas gingivalis to develop an oral vaccine. Methods: The mice were immunized orally on days 0, 7, and 14 with 40k-OMP alone, or combined with cholera toxin (CT) or CpG ODN. One week after the last immunization, mice were orally infected with P. gingivalis. Results: Oral immunization with 40k-OMP plus CpG ODN induced significant serum IgG responses that are comparable or even higher than those induced with 40k-OMP plus CT. Further, high levels of IgA anti-40k-OMP antibody (Ab) responses were induced in saliva when 40k-OMP plus CpG ODN were given orally, whereas oral immunization with 40k-OMP alone or 40k-OMP plus CT failed to induce salivary IgA anti-40k-OMP Abs. Ab-forming cell (AFC) analysis supported the Ab titers by revealing high number of 40k-OMP-specific IgA AFCs in salivary glands after oral immunization with 40k-OMP plus CpG ODN. The 40k-OMP-specific CD4⁺ T cells from spleen or cervical lymph nodes of mice given 40k-OMP plus CpG ODN showed higher proliferative responses than did mice immunized with 40k-OMP alone. Importantly, the mice immunized with 40k-OMP plus CpG ODN showed significant reduction of alveolar bone lose caused by P. gingivalis infection. Conclusion: These results suggest that oral administration of 40k-OMP together with CpG ODN could be an effective oral vaccine for prevention of P. gingivalis infection. Further, these findings reveal a promising perspective for the application of CpG ODN as a potent adjuvant for oral immunization against a wide range of infectious diseases. This work is supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science as well as by NIH grants DE 12242 and AG 025873.