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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Infectious Agents and Disease

This article is part of the Research TopicInnovative Biologics in the Battle Against Bacterial Pathogens: Disrupting Pathogenesis with PrecisionView all 3 articles

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

Provisionally accepted
Yongchuan ZhouYongchuan Zhou1Hong ShiHong Shi2Qiong GuoQiong Guo3Yue LiYue Li1Lu LvLu Lv3Lili HouLili Hou3Cong GengCong Geng3Dazhuang WangDazhuang Wang3Yu ShaoxiongYu Shaoxiong3Yilin LiYilin Li1Zhaopeng SunZhaopeng Sun3Chunlei LiChunlei Li1,3*
  • 1school of pharmacy hebei medical university, shijiazhuang, China
  • 2Hospital of Stomatology Hebei Medical University, Shijiazhuang, China
  • 3CSPC Pharmaceutical Group Co Ltd, Shijiazhuang, China

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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.

Keywords: dental caries3, Fc fusion antigen5, Heterologous prime- boost4, mRNA-LNPs vaccine1, mucosal immunity6, Streptococcus mutans2

Received: 12 Jan 2026; Accepted: 16 Feb 2026.

Copyright: © 2026 Zhou, Shi, Guo, Li, Lv, Hou, Geng, Wang, Shaoxiong, Li, Sun and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chunlei Li

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material