The goal of this study is to develop a live vector vaccine against Helicobacter pylori by expression of urease in attenuated Shigella flexneri 2A strains and testing the ability of these strains to induce a protective mucosal response against H. felis in mice. Helicobacter pylori ureases will be expressed in attenuated S. flexneri strains to assess the feasibility of Shigella as an oral vaccine vector. OraVax and others have demonstrated that oral immunization with H. pylori urease results in a protective response against H. felis infection in mice when administered along with Cholera Toxin as a mucosal adjuvant. Attenuated S. flexneri 2A (CVD1203) expressing urease will be constructed and used to immunize mice. Protective immunity to Helicobacter infection will be assessed by subsequent challenge with H. felis. The proposed experiments will evaluate the use of a live vector approach to immunization against H. pylori as an alternative to toxic mucosal adjuvants. The results of these preliminary experiments will provide the basis for Phase II experiments using non-human primate models of Shigella and H. pylori to confirm the efficacy of live attenuated S. flexneri 2A strains as vaccine live delivery vectors.
The development of an attenuated recombinant strain of Shigella with the ability to induce a high level mucosal immune response against the expressed foreign gene product could have high commercial potential. The devleopment of a vaccine directed towards preventing colonization by Helicobacter pylori could also have high commercial potential.
