STOMACH

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:
Correspondence to:
Dr D Y Graham
Veterans Affairs Medical Center, Rm 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030, USA; dgraham{at}bcm.tmc.edu

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.

Abbreviations: ¹³C-UBT, ¹³C urea breath test; IL, interleukin; OD, optical density; BCS, Baylor challenge strain

Keywords: Helicobacter pylori; challenge; vaccine; histology

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