Antimicrobial & Immunization for Bacterial Gastritis

DESCRIPTION (provided by applicant): Helicobacter pylori (Hp), a gastric bacterial pathogen of humans; infection is the cause of type B gastritis and is also strongly associated with gastric carcinoma (intestinal type) and gastric MALT lymphoma. Combination antimicrobial therapy (triple therapy with a bismuth salt, metranidazole and a broad spectrum antibiotic) is successful in 80% of Hp-infected symptomatic patients; treatment failures are expressed as recrudescence of infection and clinical signs and are associated with development of antibiotic-resistant microbes and poor patient compliance. In a previous SBIR, we have demonstrated that parenteral immunization with an Hp proteolytic digest prevents colonization in Hp-challenged gnotobiotic swine. Preliminary data suggest that activated T cells and their products, in particular, interferon gamma (IFNg), are central for this immunoprotective effect. An ideal approach to the problem of recrudescence treatment failure is to combine antimicrobial therapy with parenteral immunization in the post-treatment interval when Hp colonization levels are low to nonexistent yet the risk of eventual recurrence is real. In this SBIR proposal, we will test the hypothesis that parenteral immunizations of piglets, temporarily cleared or eradicated of infection with selected antimicrobials, will resist re-challenge inoculation with Hp. In addition, we will test the hypotheses that the mechanism of protection is, in part, mediated by IFNg and that orally administered IFNg will prevent recrudescence and may even replace current antimicrobial regimens if a positive therapeutic effect in actively infected piglets can be achieved. From these data, the feasibility of a combined antimicrobial and immunization approach for the successful treatment of symptomatic Hp disease in humans will be discerned. If these data are positive, a phase II SBIR application will be prepared to capitalize on these findings for the commercial development of this novel approach to Hp-associated gastric infection.