Challenge model for Helicobacter pylori infection in human volunteers
- D Y Graham,
- A R Opekun,
- M S Osato,
- H M T El-Zimaity,
- C K Lee,
- Y Yamaoka,
- W A Qureshi,
- M Cadoz,
- T P Monath
- VAMC and Baylor College of Medicine, Houston, TX, USA, Aventis-Pasteur, Marcy l’Etoile, France, and Acambis, Inc, Cambridge, Massachusetts, USA
- Correspondence to:
Dr D Y Graham
Veterans Affairs Medical Center, Rm 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030, USA;
- Accepted 19 February 2004
- Revised 18 February 2004
Background: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates.
Methods: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 104–1010 cfu of H pylori in beef broth the next morning. Infection was confirmed by 13C urea breath test (13C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology.
Results: Twenty subjects (nine women and 11 men; aged 23–33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >103 viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge.
Conclusion: Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.