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ABSTRACTHelicobacter pyloriinfection is relatively common worldwide and is closely related to gastric mucosa-associated lymphoid tissue (MALT) lymphoma, chronic gastritis, and stomach ulcers. Therefore, a safe and effective method for preventing H. pyloriinfection is urgently needed. Given that developing an effective vaccine against H. pyloriis one of the best alternatives, H. pyloriadhesin Hp0410 was expressed in the food-grade bacterium Lactobacillus acidophilus. The recombinant live bacterial vaccine was then used to orally vaccinate mice, and the immunoprotective effects of Hp0410-producing strains were investigated. H. pyloricolonization in the stomach of mice immunized with the recombinant L. acidophiluswas significantly reduced, in comparison with that in control groups. Furthermore, mucosal secretory IgA antibodies were elicited in the mucosal tissue of mice immunized with the recombinant bacteria, and specific anti-Hp0410 IgG responses were also detected in mouse serum. There was a significant increase in the level of protection against gastric Helicobacterinfection following a challenge with H. pyloriSydney strain 1 (SS1). Our results collectively indicate that adhesin Hp0410 is a promising candidate vaccine antigen, and recombinant L. acidophilusexpressing Hp0410 is likely to constitute an effective, low-cost, live bacterial vaccine against H. pylori.