Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys

Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 mu g Escherichia coli heat-labile ent erotoxin (LT) or immunized with LT alone. An initial 6 doses were administe red over an 8 week period. All five vaccinated monkeys had a greater than t wofold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori col onization. H. pylori was eradicated from these monkeys with a course of ant imicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H, pylori. Necropsy was perfo rmed 23 weeks after rechallenge and H. pylori colonization was determined b y histological examination of 12 individual gastric sites. A significant re duction in colonization (p less than or equal to 0.0001; Friedman's analysi s of variance) was found in the vaccinated animals. Histopathologic examina tion of necropsy tissues also revealed a trend towards reduced gastritis an d epithelial alterations in the vaccinated group compared to animals receiv ing LT alone. This study provides the first evidence for effective vaccinat ion of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gas tric inflammation. (C) 1999 Elsevier Science Ltd. All rights reserved.