Oral immunization with urease and Escherichia coli heat-labile enterotoxinis safe and immunogenic in Helicobacter pylori-infected adults

Background & Aims: Oral immunization with Helicobacter pylori urease can cu re Helicobacter infection in animals. As a step toward therapeutic immuniza tion in humans, the safety and immunogenicity of oral immunization with rec ombinant H, pylori urease were tested in H. pylori-infected adults. Methods : Twenty-six H. pylori-infected volunteers were randomized in a double-blin d study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 mu g heat-labile enterotoxin of Escherichia coil (LT), LT alone, or placebo. S ide effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for h istology and quantitative cultures. Results: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study, Antiurease serum immunogl obulin A titers increased 1.58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fol d (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively , whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circ ulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13.6/10(6) vs. 5.4 +/- 3 .1; P 0.018). Eradication of H. pylori infection was not observed, but urea se immunization induced a significant decrease in gastric H. pylori density . Conclusions: H. pylori urease with LT is well tolerated and immunogenic i n H. pylori-infected individuals. An improved vaccine formulation may induc e curative immunity.