Animal models and vaccine development.

Abstract

Following the demonstration of Helicobacter pylori as a major gastroduodenal pathogen there was a need to develop animal models in order to investigate mechanisms of pathogenesis and to be able to test new treatment strategies. Helicobacter pylori will only colonize a limited number of hosts including non-human primates, germ-free or barrier raised piglets, germ-free dogs and recently laboratory raised cats. Although these models have proved useful there is a need for more convenient small animal models. The ferret infected with its natural gastric organism, Helicobacter mustelae, is the only other animal to show peptic ulceration and has been successfully used to investigate gastritis and antimicrobial agents. The other commonly used animal model is the laboratory mouse or rat infected with either Helicobacter felis or Helicobacter heilmannii, bacteria that normally colonize cat or dog gastric mucosae. Active/chronic gastritis, gastric atrophy, and lymphoma-like lesions have been shown to develop in H. felis infected mice. The most recent and exciting use of an animal model has been the use of the H. felis mouse model in the development of human vaccines against H. pylori. Mice can be protected against infection with large doses of viable H. felis by oral immunization using sonicates of H. felis or H. pylori or recombinant H. pylori urease together with cholera toxin or cholera toxin-B subunit as the mucosal adjuvant. More importantly it has been shown that immunization of already infected animals results in eradication of infection. This raises the intriguing possibility that therapeutic immunization might be a viable option in the management of Helicobacter-associated disease. If immunization as a therapy of peptic ulcers was combined with short-term acid suppression, the possibility of reinfection may also be eliminated. In those countries where H. pylori infection rates are very high and infection occurs at an early age, large scale oral immunization of sections of the community would not only protect the young from the deleterious consequences of long-term H. pylori infection but could also cure existing disease.