We previously demonstrated that an anti-caries DNA vaccine intranasally administered with recombinant flagellin protein as a mucosal adjuvant enhanced salivary IgA response and conferred better protection against caries. However, the relatively weak immunogenicity of DNA vaccines and the necessity for a large quantity of antigens remain significant challenges. Here, we fused the flagellin derived from E. coli (KF) and target antigen PAc containing the A-P fragment of PAc from S. mutans (rPAc) to produce a single recombinant protein (KF-rPAc). The abilities of KF-rPAc to induce rPAc-specific mucosal and systemic responses and protective efficiency against caries following intranasal immunization were compared with those of rPAc alone or a mixture of rPAc and KF (KF + rPAc) in rats. Results showed that KF-rPAc promoted significantly higher rPAc-specific antibodies in serum as well as in saliva than did an equivalent dose of rPAc alone or a mixture of KF + rPAc. Intranasal immunization of 8.5 µg KF-rPAc could achieve 64.2% reduction of dental caries in rats. In conclusion, our study demonstrated that flagellin and PAc fusion strategy is promising for anti-caries vaccine development, and KF-rPAc could be used as an anti-caries mucosal vaccine.

We and others have shown that anti-caries DNA vaccines, including pGJA-P/VAX, are promising for preventing dental caries. However, challenges remain because of the low immunogenicity of DNA vaccines. In this study, we used recombinant flagellin protein derived from Salmonella (FliC) as a mucosal adjuvant for anti-caries DNA vaccine (pGJA-P/VAX) and analyzed the effects of FliC protein on the serum PAc-specific IgG and saliva PAc-specific IgA antibody responses, the colonization of Streptococcus mutans (S. mutans) on rat teeth, and the formation of caries lesions. Our results showed that FliC promoted the production of PAc-specific IgG in serum and secretory IgA (S-IgA) in saliva of rats by intranasal immunization with pGJA-P/VAX plus FliC. Furthermore, we found that enhanced PAc-specific IgA responses in saliva were associated with the inhibition of S. mutans colonization of tooth surfaces and endowed better protection with significant fewer caries lesions. In conclusion, our study demonstrates that recombinant FliC could enhance specific IgA responses in saliva and protective ability of pGJA-P/VAX, providing an effective mucosal adjuvant candidate for intranasal immunization of an anti-caries DNA vaccine.

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