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Because of the high prevalence of Helicobacter pylori infection and the morbidity and mortality associated to the disease, development of a preventive vaccine has become a priority. To this goal, we produced recombinant H. pylori urease B (rUreB) and tested its immunogenicity in BALB/c mice when administered as 3 doses (week 0, 4 and 6) by either parenteral (intramuscular) or mucosal routes (intragastric, intranasal, intrarectal) and with the use of various adjuvants (none, CpG, alum or Freund’s). The intramuscular route was more immunogenic than any mucosal route; of the mucosas, only intranasal induced modest levels of serum IgG. All adjuvants improved the seroresponse to plain rUreB and, of them, Freund’s and alum were equally good and better than CpG ODN 1826. Stool IgA was barely detected by any immunization strategy.