Helicobacter pylori infection is a major risk factor for chronic gastritis, digestive ulcers, gastric adenocarcinoma and lymphoma. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. Bacillus subtilis is non-pathogenic and can produce endospores, which can survive under extreme conditions. These features make the B. subtilis spore an ideal vehicle for delivery of heterologous antigens to extreme environments such as the gastrointestinal tract. In this study, we displayed H. pylori urease B protein on the B. subtilis spore coat using the spore coat protein CotC as a fusion partner. Western blot analyses were used to verify urease B surface expression on spores. Recombinant spores displaying the urease B antigen were used for oral immunization and were shown to generate humoral response in mice. Urease B-specific secretory IgA in faeces and IgG in serum reached significant levels 2 weeks after oral dosing. In addition, oral immunization of recombinant urease B spores induced a significant reduction (84 %) in the stomach bacterial load (0.25±0.13×10(6) c.f.u.) compared to that in the non-recombinant spores treated group (1.56±0.3×10(6) c.f.u.; P<0.01). This report shows that urease B expressed on B. subtilis spores was immunogenic, and oral administration of urease B spores can provide protection against H. pylori infection.