The oral cavity is structurally considered to be an organ that provide double layers of protection simultaneously through secretory immunoglobulin A (S-IgA) from mucosal immunity and immunoglobulin (Ig) G antibodies (Abs) from gingival crevicular fluid (1-3). Although immunization via injection can induce an effective immune responses in the systemic immune systems, but not an antigen (Ag)specific mucosal immune responses. Therefore, in order to prevent oral infection, it is ideal to induce mucosal immunity and systemic immunity simultaneously. Chronic periodontitis reduces oral function by causing periodontal tissue destruction and bone resorption. Recently, chronic periodontitis has been reported to cause systemic diseases such as diabetes, aspiration pneumonia, and atherosclerosis, and their relationship has been investigated (4-9). Therefore, prevention of periodontitis is important for oral health and systemic health derived from the oral cavity. Currently 7 to 10 bacterial candidates have been claimed to be putative periodontal pathogens (10, 11). Among them, P. gingivalis is a keystone pathogen that is strongly associated with disease progression of chronic periodontitis. The reason for using GroEL as a vaccine antigen is that is can be found in most putative periodontopathic pathogens, including P.gingivalis, and it was reported to crossreact among bacterial antigens. Thus far, a positive relationship has been observed between levels of saliva IgA directed against GroEL and

It has been reported that GroEL, a heat shock protein (HSP) produced by the representative periodontopathogenic bacterium, Porphyromonas gingivalis, induces inflammation-induced osteoclastogenesis and promotes alveolar bone resorption. In this study, we demonstrated the efficacy of a mucosal vaccine targeting GroEL against bone resorption induced by P. gingivalis. Female BALB/c mice received sublingual CpG oligodeoxynucleotide as an adjuvant with recombinant GroEL (rGroEL) prior to P. gingivalis exposure. Animals were euthanized 30 days after P. gingivalis inoculation.Sublingual immunization (SLI) with rGroEL elicited significant rGroEL-specific serum immunoglobulin (Ig)G and salivary IgA antibody (Ab) responses, and these responses were sustained for approximately 1 year. Interestingly, 10-fold more GroEL-specific IgA Ab-producing cells were detected in the submandibular glands (SMGs) than in the spleen. Antigen (Ag)-specific cells isolated from the spleen and SMGs induced significantly higher levels of IFN-γ expression after Ag restimulation in vitro. Flow cytometry illustrated that the frequency of CD11b + dendritic cells with enhanced expression of CD80, CD86, CD40, and major histocompatibility complex II molecules was significantly increased in the SMGs. Furthermore, SLI with rGroEL significantly suppressed P. gingivalis-induced alveolar bone resorption and P. gingivalis-stimulated tumor necrosis factor-α, interleukin-6, and HSP60 expression in the gingiva.These findings suggest that SLI with rGroEL and CpG oligodeoxynucleotide is a beneficial strategy for preventing periodontal disease, mainly by presenting Ags in the oral region and inducing antibody production in the mucosal and systemic systems.