Preclinical evaluation of an mRNA-LNPs vaccine for mucosal protection against dental caries.

OBJECTIVE: Despite the success of mRNA-LNPs vaccines against viruses, their potential against prokaryotic pathogens remains underexplored. We provide proof-of-concept for an mRNA-LNPs vaccine against Streptococcus mutans (S. mutans), the primary cause of dental caries. METHODS: We constructed LNPs-encapsulated mRNA vaccines encoding S. mutans PAc antigen alone or PAc fused with human IgG Fc domain, aiming to enhance mucosal immunity via Fc-FcRn interactions. RESULTS: A heterologous intramuscular prime-intranasal boost regimen induced robust, durable (>4 months) sIgA responses-2.6-fold higher with Fc fusion-that significantly inhibited S. mutans biofilm formation in vitro and reduced moderate dentinal caries by >60% in rats. CONCLUSION: Bacterial antigens can be effectively delivered via mRNA platforms, and Fc fusion is a promising strategy to enhance mucosal immunity against oral, respiratory, and other mucosal pathogens, consistent with Fc-FcRn-mediated mechanisms.