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

## TL;DR

This study shows that an mRNA vaccine can protect against dental caries by boosting mucosal immunity in rats.

## Contribution

The study introduces an mRNA-LNPs vaccine with Fc fusion to enhance mucosal immunity against S. mutans.

## Key findings

- The vaccine induced durable sIgA responses and inhibited S. mutans biofilm formation.
- Fc fusion increased sIgA responses by 2.6-fold and reduced dentinal caries by over 60% in rats.

## Abstract

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.

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.

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.

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.