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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1697591

This article is part of the Research TopicInnovative Adjuvant Strategies: Enhancing Vaccine Efficacy Through Transdisciplinary ApproachesView all 10 articles

Gram-positive enhancer matrix delivering FVpE via M cell targeting elicit protective mucosal and adaptive immune responses against Helicobacter pylori infection

Provisionally accepted
Fu  rui ZhangFu rui Zhang1Ya  qin HeYa qin He2Jing  WuJing Wu1Jia  le ChenJia le Chen1Xin  LiXin Li1Lin  han NiLin han Ni1Zhen  ZhangZhen Zhang2JUAN  CHENJUAN CHEN2Kunmei  LiuKunmei Liu1Le  GuoLe Guo1,2*
  • 1Ningxia Medical University, Yinchuan, China
  • 2General Hospital of Ningxia Medical University, Yinchuan, China

The final, formatted version of the article will be published soon.

Background: The Gram-positive enhancer matrix (GEM) is a novel mucosal vaccine delivery system based on lactic acid bacteria (LAB). Helicobacter pylori (H. pylori) mainly colonize the gastric mucosa and thus induce various gastric diseases. Hence, the development of an efficient mucosal vaccine is expected to be a new strategy for the prevention and treatment of H. pylori. Methods and Results: This study is based on the GEM delivery system, which constructs an oral vaccine targeting intestinal M cells, GEM-SAM-FVpE. Here, SAM represents the surface anchoring protein (cA) and the M cell-targeting peptide (Mtp), thereby enabling both efficient display on the GEM particle and targeted to intestinal M cells. And FVpE denotes the H. pylori multi-epitope antigen. As a results, GEM is able to successfully display the purified antigen SAM-FVpE on the surface, with a display efficiency of 90%. Meanwhile, GEM-SAM-FVpE enhances antigen presentation efficiency and activates DCs by upregulating MHC II and costimulatory molecules (CD80/CD86/CD40), and increasing the secretion of related cytokines. In vivo experiments indicate that oral administration of the GEM-SAM-FVpE significantly induces the production of high titers of sIgA, serum IgG, and its subtype, initiating mucosal and humoral immune responses, and inhibiting the adhesion of H. pylori to normal gastric mucosal epithelial cells. In addition, by significantly activating Th1, Th2, and Th17, it initiates antigen-specific cellular immune responses. Finally, H. pylori-infected mice treated with GEM-SAM-FVpE can significantly reduce the colonization of H. pylori in gastric tissue while also decreasing gastric mucosal damage. Conclusion: GEM-SAM-FVpE can effectively induce protective mucosal responses and adaptive immune responses against H. pylori infection, providing a new scheme for the development of oral vaccines against H. pylori.

Keywords: Gram-positive enhancer matrix, H. pylori, M cells, Mucosal immune, Adaptive immune

Received: 02 Sep 2025; Accepted: 15 Oct 2025.

Copyright: © 2025 Zhang, He, Wu, Chen, Li, Ni, Zhang, CHEN, Liu and Guo. 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: Le Guo, guole@nxmu.edu.cn

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