OBJECTIVE Protein of Streptococcus mutans is considered as one of the virulence factors due to its ability to mediate the initial attachment of Streptococcus mutans to tooth surface. In this study, an anticaries DNA vaccine pCIA-P was used to immunize rats. The expression of PAc in different tissues in vivo, specific immune response and protection effects against dental caries were observed. METHODS Plasmid pCIA-P was injected into rats by two different routs: intramuscular injection (i.m.) and targeted salivary gland immunization (TSG). Immunohistochemistry technique was used to detect the expression of PAc. Gnotobiotic rats were vaccinated with pCIA-P by three different approaches: TSG, intramuscular injection and buccal mucosal injection (i.o.). The specific immune responses were evaluated by ELISA and their anticaries effects were evaluated by Keyes caries scores. RESULTS PAc was expressed in the sarcoplasm and sarcolemma of muscle fibers and submandibular glands, especially strongly positive in duct regions. The levels of serum specific anti-PAc IgG and salivary specific anti-PAc IgA in TSG immunization and buccal mucosal immunization group were significantly higher than those of other groups. The Keyes caries scores of those two groups were significantly lower than those of other groups. CONCLUSIONS The plasmid pCIA-P could provoke specific immune responses as a novel immunogen. Mucosal immunization with pCIA-P appears to be an effective genetic immunization method against dental caries.