A preventive LNP-mRNA vaccine encoding a truncated form of OipA conferred protection against Helicobacter pylori challenge in BALB/c mice

Helicobacter pylori ( H. pylori ) infection is associated with a spectrum of gastric diseases, ranging from chronic atrophic gastritis to gastric ulcers, and potentially gastric cancer. The outer membrane protein of H. pylori plays a significant role in its pathogenicity. Although the global incidence of H. pylori infection has declined in recent years, the rise in antibiotic resistance is far from optimistic, highlighting the urgent need for new prevention strategies. Herein we identified the sequence of outer inflammatory protein A (OipA) in H. pylori using mass spectrometry, then two extracellular functional fragments were selected based on the consistency of B-cell and T-cell epitope scores to construct the truncated OipA antigen (Trunc OipA). Based on this fragment (Trunc OipA), we developed a prophylactic lipid nanoparticles (LNPs) formulated mRNA vaccine targeting OipA. After intramuscular immunization in BALB/c mice, the vaccine induced a strong anti OipA specific humoral response, as well as a mixed T helper cell 1/T helper cell 2 (Th1/Th2) cytokine profile and a moderate increase in the proportion of CD8 + T cells in the spleen. Subsequently, this vaccine reduced the colonization of H. pylori and provided protection at least three months following H. pylori challenge, simultaneously demonstrating no pathological change of organs, or damage to cardiac and kidney function. Overall, these data indicate that the OipA LNP-mRNA vaccine is immunogenic and confers protective immunity in mice for at least three months; however, further optimization is needed before clinical translation.