2009 Volume 7 Issue 3 Pages 143-151
Our previous study has demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli (mCTA/LTB) elicited a long-term protective immune response. Although using adjuvant mCTA/LTB gave comparable Ab responses in the saliva as using native cholera toxin as adjuvant, the total IgE and 40k-OMP-specific IgE antibodies, as well as IL-4 levels induced by mCTA/LTB were lower than those induced by native cholera toxin. In this study, we further elucidated the nature of 40k-OMP-specific CD4+ T helper cells in immunized mice. When CD4+ T cells isolated from cervical lymph nodes and spleens of mice immunized with 40k-OMP plus mCTA/LTB as adjuvant were restimulated with 40k-OMP in vitro, significant levels of proliferation occurred in cervical lymph nodes and spleens. Furthermore, mCTA/LTB as adjuvant induced 40k-OMP-specific CD4+ T cells secreting INF-γ and IL-4-independent IL-5, IL-6, and IL-10, with IgG2a antibody responses. Analysis of IL-12 receptor expression showed that native cholera toxin, but not the mCTA/LTB, suppressed IL-12 receptor expression by activated T cells. These results suggest that mCTA/LTB as an adjuvant regulates IL-12 receptor expression and subsequent T helper cytokine responses in oral mucosal compartments and that nasal administration of 40k-OMP plus mCTA/LTB is an effective mucosal vaccine against oral infection by P. gingivalis.
