P>Aim To construct a dendritic cell (DC)-targeted DNA vaccine against FimA of Porphyromonas gingivalis and evaluate the immunogenicity and protection in mice. Materials and Methods A targeted DNA plasmid pCTLA4-FimA, which encodes the signal peptide and extracellular regions of mouse cytotoxic T lymphocyte-associated antigen 4 (CTLA4), the hinge and Fc regions of human Ig gamma 1 and FimA of P. gingivalis, was constructed. Mice were immunized with pCTLA4-FimA, the non-targeted DNA plasmid pFimA, which contains only fimA gene, or pCI vector intra-nasally. Serum and saliva antibody responses were detected by enzyme-linked immunosorbent assay. The protection against P. gingivalis-induced periodontitis was evaluated by measuring alveolar bone loss in mice. Results Mice immunized with pCTLA4-FimA showed elevated levels of specific serum IgG and salivary IgA antibody responses compared with mice immunized with pFimA (p < 0.01). Both pFimA and pCTLA4-FimA immunized groups showed significantly lower alveolar bone loss, with the magnitude protection greater in the latter (p < 0.01), compared with the pCI immunized group. Conclusions The DC-targeted DNA construct pCTLA4-FimA enhanced both systemic and mucosal immunity following intra-nasal immunization. A DNA-based immunization strategy may be an effective way to attenuate periodontitis induced by P. gingivalis.