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

Gastroenterology. 1999 Apr;116(4):804-12. doi: 10.1016/s0016-5085(99)70063-6.


Background & 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 microg 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. 6/10(6) 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Bacterial Toxins / immunology*
  • Bacterial Vaccines / adverse effects
  • Bacterial Vaccines / immunology*
  • Double-Blind Method
  • Enterotoxins / immunology*
  • Escherichia coli Proteins*
  • Female
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / immunology*
  • Humans
  • Immunization / adverse effects
  • Immunoglobulin A / blood
  • Male
  • Middle Aged
  • Stomach / microbiology
  • Urease / immunology*


  • Bacterial Toxins
  • Bacterial Vaccines
  • Enterotoxins
  • Escherichia coli Proteins
  • Immunoglobulin A
  • heat-labile enterotoxin, E coli
  • Urease