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

Abstract

Background and Aims: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. Methods: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 μg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. Results: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1.58-fold ± 0.37-fold and 3.66-fold ± 1.5-fold (mean ± SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo ± LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 ± 13.6/106 vs. 5.4 ± 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. Conclusions: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.