BACKGROUND: The development of an efficacious vaccine against infection with Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma, remains a challenge. Since the use of mucosal adjuvants is limited in human application, we have evaluated the potential of recombinant Lactobacillus strains producing H. pylori urease B (UreB) subunit to deliver this antigen to the gastrointestinal tract. METHODS: Mice were injected orally 3 times with a triple dose of recombinant Lactobacillus plantarum NCIMB8826, the recombinant isogenic cell-wall mutant (alr(-) MD007 strain) expressing UreB, or a mixture of recombinant UreB and cholera toxin (rUreB/CT) as a control. Urease-specific seric immunoglobulin (Ig) G and IgA were measured by use of an enzyme-linked immunosorbent assay. After challenge with Helicobacter felis, stomach infection was examined by use of the rapid urease test and by polymerase chain reaction detection of Helicobacter genomic DNA. RESULTS: Intragastric immunization with both recombinant Lactobacillus strains and rUreB/CT elicited UreB-specific antibodies. After challenge, reduction of H. felis load in the stomachs of mice was observed only after immunization with the recombinant mutant strain MD007 or with rUreB/CT. CONCLUSIONS: This is the first report of successful induction of partial protection against H. felis with a mucosal prime-boost regimen in which recombinant Lactobacillus strains were used as antigen-delivery vehicles.