PROTECTION OF MICE AGAINST GASTRIC COLONIZATION BY HELICOBACTER-PYLORI BY SINGLE ORAL DOSE IMMUNIZATION WITH ATTENUATED SALMONELLA-TYPHIMURIUM PRODUCING UREASE SUBUNIT-A AND SUBUNIT-B

Helicobacter pylori is a Gram-negative bacterial pathogen associated w ith gastritis, peptic ulceration, and gastric carcinoma. The bacteria express a strong urease activity which is known to be essential for co lonization of gnotobiotic pigs and nude mice. UreA and UreB, two struc tural subunits of the active enzyme were expressed in the attenuated S almonella typhimurium live vaccine SL3261 strain. Evaluation of protec tion against H. pylori was performed in Balb/c mice by oral immunizati on with a single dose of the vaccine strain. Five weeks after immuniza tion, mice were challenged orally three times with a mouse-adapted H. pylori wild type strain and, six weeks later mice were sacrificed to d etermine H. pylori infection by detection of urease activity from the antral region of the mouse stomachs, In several independent experiment s, we observed 100% infection with H. pylori in the non-immunized mice and no infection (100% protection) in the mice immunized with S. typh imurium expressing recombinant UreA and UreB. Specific humoral and muc osal antibody responses against UreA and UreB were observed in mice im munized as indicated by western blots and ELISA assays, These data sho ws that oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain induced a specific immune response and p rotected mice against H. pylori colonization. Single oral dose immuniz ation with UreA and UreB delivered by a live Salmonella vaccine vector appears to be an attractive candidate for human vaccination against H . pylori infection. In addition, this model will aid to elucidate the effective protection mechanisms against H. pylori in the gastric mucos a. (C) 1998 Elsevier Science Ltd. All rights reserved.