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.
Zhou et al. (Tue,) studied this question.