SBIR-STTR Award

The goal is to determine the feasibility of oral vaccination with recombinant Helicobacterpylori urease. This goal will be tested by the oral immunization of germ and specific pathogen free mice with recombinant urease fusion proteins in formulations designed to elicit mucosal immune responses. The gastric immune response to the vaccination will be confirmed. Protection will be assessed by gastric chalfenge with H. felis. H. pylori infections of humans have been shown to cause chronic gastritis and peptic ulcer disease. Treatment of these conditions currently involves the use of compounds to reduce stomach acid as well as antibiotic therapies to eradicate the bacterium. These approaches have been met with limited success and recurrence of disease is common. Immunization to prevent infection by these organisms is a novel approach to prevent the occurrence of these diseases rather than reliance on marginally effective treatments. The results of these preliminary experiments will provide a basis for Phase II experiments in non-human primates. The experiments will use a direct challenge with H. pylori to confirm the efficacy of vaccination in the prevention gastric.Awardee's statement of the potential commercial applications of the research: Helicobacter pylori infection is a major cause of gastritis as wefl as duodenal and gastric ulcers. The U. S. market for anti-ulcer drugs is $5 billion for the year 1992. An effective vaccine that prevents primary infections in children or young adults would pose a tremendous savings in medical costs and human suffering.National Institute of Allergy and Infectious Diseases (NIAID)

We will develop mucosally administered vaccines against Helicobacter pylori infection to prevent the consequences of chronic H. pylori infection which may include gastritis, duodenal ulceration, and gastric carcinoma. One vaccine would dicit an immune response that would protect against primary infection and a second vaccine would dicit an immune response that would assist an infected individual in clearing the infection. Our Phase I study showed that immunization with a recombinant urease apoenzyme from H. pylori protected mice against challenge with Helicobacter felis.- Phase II has several specific aims: (i) confirm and more fully characterize these observations in mice by determining dose requirements, route of immunization, requirement for adjuvants, duration of protection and mechanism of protection; (ii) extend the observation on urease in H. pylori animal models, and (iii) conduct a clinical trial to assess tolerability and to obtain data on immunogenicity in humans.National Institute of Allergy and Infectious Diseases (NIAID)