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

幽门螺杆菌（Helicobacter pylori）是一种革兰氏致病菌，在全世界一半人口的胃粘膜中慢性感染。持续感染可诱发胃炎和消化性溃疡，并增加发生胃腺癌和malt淋巴瘤的风险。感染的治疗是基于使用两种抗生素和质子泵抑制剂的三联疗法。当加入霍乱毒素（CT）或热不稳定的大肠杆菌毒素（LT）作为粘膜佐剂时，重组幽门螺杆菌蛋白，如脲酶、过氧化氢酶或细胞毒素，在幽门螺杆菌小鼠模型中是有效的。表达幽门螺杆菌脲酶的活沙门氏菌菌株在没有额外佐剂的情况下可以防止幽门螺杆菌侵袭感染。我们提出了一种新的幽门螺杆菌鬼魂方法，幽门螺杆菌鬼魂是幽门螺杆菌中phiX裂解基因盒控制表达产生的空细菌包膜。鬼蛋白的表面结构完整，含有黏附素和脂多糖，对免疫系统来说，比分离的蛋白质更稳定。我们希望优化幽门螺杆菌鬼作为有效的疫苗工作，没有额外的粘膜佐剂。如果需要进一步的粘膜佐剂，将产生重组鬼影，要么表达CT的解毒版本，要么在表面表达耶尔森菌入侵，以刺激或调节免疫系统。

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.