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It is well establishedthat Porphyromonas gingivalisis one of the major pathogens of adult periodontitis. P. gingivalis produces an outer membrane protein with a molecular mass of 40-kDa (40k-OMP). In the present study, in order to assess the potential for application of 40k-OMP in the development of an antiperiodontal disease vaccine, we analyzed 40k-OMP-specific CD4+ T helper (Th) cell responses induced in the mucosal as well as systemic compartments when 40k-OMP was administered nasally. When CD4+T cells that were isolated from cervical lymph nodes (CLN) and spleens of mice immunized with 40k-OMP plus cholera toxin (CT) as adjuvant were re-stimulated with 40k-OMP in vitro, significant levels of proliferative responses were induced. In contrast, essentially no increased proliferation occurred in CLN and spleens taken from mice given 40k-OMP alone. Analysis of T helper (Th) 1 (IFN-y) and Th2 (IL-4, IL-5 and IL-6) cytokine responses showed that 40k-OMP-specific Th cells from both CLN and the spleen produced significant levels of IL-4, IL-5 and IL-6 but did not result in changes in IFN-y production. In contrast, marginal levels of IL-4, IL-5 and IL-6 production were seen in mice given 40k-OMP alone nasally. These results suggest that nasal administration of 40k-OMP plus CT as an adjuvant can elicit 40k-OMP-specific Th2-type cytokine responses in both mucosal and systemic compartments. Further, the nasal 40k-OMP vaccine possesses the potential for antiperiodontal vaccine.

It is well established that cholera toxin (CT) produced by Vibrio cholerae acts as a potent mucosal adjuvant; however, the native form of this molecule causes severe diarrhea. Furthermore, both native CT and its B-subunit derivative bind to monosialogangliosides (GM1) in membrane raft microdomains on neural tissues and are thus unsuitable for use in humans. In this study, we evaluated the adjuvanticity of the CT A-subunit (CT-A) administered with ovalbumin (OVA) by the nasal route. We found that nasal administration of OVA plus CT-A elicited both mucosal and systemic antibody (Ab) responses. Immunization of mice with OVA plus CT-A resulted in the induction of OVA-specific IgA Abs in saliva and nasal secretions. Furthermore, significant OVA-specific serum immunoglobulin (Ig) G and IgA Ab responses were induced. Antibody-forming cell (AFC) analysis confirmed the Ab titer findings by revealing significant numbers of OVA-specific IgA AFCs in submandibular glands. In addition, splenic lymphocytes restimulated with OVA in vitro exhibited significant proliferative responses. Thus, CT-A might be a candidate for an effective adjuvant for inducing antigen (Ag)-specific Ab responses in human systemic and mucosal compartments, such as the oral cavity.

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