Vaccination against Helicobacter pylori with gamma-glutamyltranspeptidase

Helicobacter pylori (H.p.) is the most widespread bacterial infection, affecting half of the world population and causing peptic ulcers and gastric cancer. Although big efforts have been initiated to develop a vaccine against this pathogen none of these experimental approaches led to successful results in human studies and thus failed to generate an approved vaccine in humans. It is unclear if this is due to the antigens used, the vaccine formulations tested to induce protective immunity or the laboratory infection models applied. Our group described a virulence factor of H. pylori, the H.p. gamma-glutmyltranspeptidase (HPgGT) that inhibits the proliferation of T-cells and thus prevents the generation of an effective immune response. We used HPgGT in an experimental mouse infection model for a novel vaccination approach. Immunization with this antigen induces strong antibody responses, which blocks its enzymatic activity, thereby counteracting the immunosuppressive activity of HPgGT. Different formulations and routes of application were tested, revealing a need for mucosal immunization. As HPgGT is a secreted protein, HPgGT specific T-cells can hardly target the pathogen. Therefore we combine this protein with outer membrane proteins to induce protective T-cell responses. In infection experiments this vaccination lead to a substantial decrease of bacterial colonization in the stomach, making this new approach of a “liberating vaccine“ a promising candidate for a new immunization strategy.