Optimisation of recombinant Helicobacter pylori Ghosts for vaccination in H. pylori mouse and Mongolian Gerbil models

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Helicobacter pylori is a Gram-genative bacterial pathogen, which chronically infects the gastric mucosa of half of the world s population. The persistent infection induces gastritis and peptic ulceration and enhances the risk to develop stomach adenocarcinoma and MALT-Lymphoma. Treatment of the infection is based on a triple therapy using two antibiotics and a proton pump inhibitor. Vaccination by recombinant H.pylori proteins, like urease, catalase or cytotoxin, is efficient in the H.pylori mouse model when cholera toxin (CT) or heat labile E. coli toxin (LT) is added as a mucosal adjuvant. Live Salmonella strains expressing H.pylori urease protect against a H pylori challenge infection without additional adjuvants. We present a novel approach with H.pylori ghosts, which are empty bacterial envelopes generated by the controlled expression of the phiX lysis gene cassette in H. pylori. Ghosts present a structurally intact surface containing adhesins and LPS to the immune system and are more stable compared to isolated proteins. We hope to optimise H. pylori ghosts to work as efficient vaccine without an additional mucosal adjuvant. If further mucosal adjuvants should be necessary, recombinant ghosts will be generated, either expressing a detoxified version of CT or a Yersinia invasin on the surface, to stimulate or modulate the immune system.