Protective immunity against Helicobacter pylori induced by a single dose of an mRNA-based UreB vaccine candidate in mice

Background Helicobacter pylori ( H. pylori ) is a global public health concern because of its strong ability to colonise the gastrointestinal tract. Current clinical therapeutic strategies are limited by antibiotic resistance, reinfection and a high recurrence rate after eradication. Therefore, effective preventive vaccines against H. pylori infections are needed to counter the potential threat of a global pandemic. Recently, mRNA vaccines have emerged as promising platforms for the prevention of major infectious diseases. UreB is regarded as a critical virulence factor in H. pylori and serves as a key vaccine candidate target. This study aimed to investigate the immunogenicity of an mRNA-based agent against H. pylori . Methods We generated an mRNA-based H. pylori vaccine candidate targeting UreB. The expression levels of LNP/mRNA-UreB in transfected HepG2 cells in vitro were characterised via Western blot, immunofluorescence, flow cytometric and sandwich ELISA. BALB/c mice were vaccinated with a single dose of LNP/mRNA-UreB to evaluate its immunogenicity and immune protective efficacy against H. pylori . Both humoral and cellular immune responses induced by LNP/mRNA-UreB were measured via ELISA, followed by challenge with H. pylori to validate the immune protective efficacy. Results LNP/mRNA-UreB was highly expressed in HepG2 cells; additionally, the molecular weight of the UreB antigen ranged from approximately 80–90 kDa, and the quantitative expression concentration was determined to be 902 pg/mL. Furthermore, mice vaccinated with LNP/mRNA-UreB via a single dose exhibited robust UreB-specific humoral immune responses with markedly elevated antibody levels and a significant Th1/Th2 mixed cellular immune response. Finally, in mice vaccinated with LNP/mRNA-UreB and subsequently infected with H. pylori SS1, gastric colonisation and urease levels were effectively reduced, demonstrating that LNP/mRNA-UreB was a promising vaccine candidate against H. pylori infection. Conclusions The LNP/mRNA-UreB vaccine candidate developed in this study represents a proof-of-concept for effective protection against H. pylori infection and mediates balanced humoral and cellular immune responses. Moreover, mRNA-based techniques may constitute a universal approach for the development of H. pylori vaccines.