MRNA-LNP Vaccines Targeting a UreB199-338 Epitope Elicit Protective Immunity Against Helicobacter pylori Infection

Background Helicobacter pylori ( H. pylori ) infection is a major global health burden associated with chronic gastritis, peptic ulcer disease, and gastric cancer. The increasing prevalence of antibiotic-resistant strains underscores the urgent need for effective prophylactic vaccination. In this study, we developed a novel mRNA-LNP vaccine platform targeting the urease subunit (UreB _{199 − 338} ), which is a key virulence factor of H. pylori . Three mRNA-LNP constructs were designed, each expressing a UreB antigen fragment fused with distinct molecular adjuvants: IFN‑γ (LUI), a polymeric IgZ domain (LUZ), or both (LUZI) to direct and enhance immune responses. We also prepared a conventional aluminum-adjuvanted recombinant protein vaccine (UreB _{199 − 338} ) and preliminarily evaluated its immunogenicity.. Results All vaccine candidates demonstrated excellent safety profiles in murine models. The mRNA-LNP vaccines elicited robust antigen-specific humoral immunity, and the induced antibodies effectively inhibited H. pylori adhesion to gastric epithelial cells in vitro. Notably, mRNA vaccines triggered a strong Th1-biased cellular immune response, characterized by significantly increased antigen-specific IFN‑γ production and elevated proportions of CD4⁺ and CD8⁺ T cells. The Alum-UreB _{199 − 338} protein vaccine also induced humoral and cellular immunity in mice. Following challenge with live H. pylori , all vaccinated groups showed a significant reduction in gastric bacterial colonization and amelioration of inflammatory pathology compared to the controls. Conclusions This study demonstrates that the UreB _{199 − 338} based mRNA-LNP vaccine platform can effectively induce both functional humoral immunity and a Th1‑polarized cellular response, resulting in significant protection against H. pylori infection. These findings highlight the potential of engineered mRNA vaccines as a promising strategy for preventing H. pylori -associated diseases. Further optimization of antigen design and delivery may enhance the translational potential of this approach.