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

重组幽门螺杆菌幽灵在幽门螺杆菌小鼠和蒙古沙鼠模型中疫苗接种的优化

• 批准号: 5266402
• 负责人: Professor Dr. Rainer Haas
• 金额: --
• 依托单位: Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5266402?language=en
• 关键词: Optimisation; recombinant; Helicobacter; pylori; Ghosts

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.

幽门螺杆菌是一种革兰氏菌病原体，长期感染世界一半人口的胃粘膜。持续感染会诱发胃炎和消化性溃疡，并增加患胃腺癌和 MALT 淋巴瘤的风险。感染的治疗基于使用两种抗生素和质子泵抑制剂的三联疗法。当添加霍乱毒素 (CT) 或不耐热大肠杆菌毒素 (LT) 作为粘膜佐剂时，重组幽门螺杆菌蛋白（如尿素酶、过氧化氢酶或细胞毒素）的疫苗接种在幽门螺杆菌小鼠模型中是有效的。表达幽门螺杆菌尿素酶的活沙门氏菌菌株可防止幽门螺杆菌攻击感染，无需额外佐剂。我们提出了一种利用幽门螺杆菌鬼影的新方法，幽门螺杆菌鬼影是由幽门螺杆菌中 phiX 裂解基因盒的受控表达产生的空细菌包膜。鬼影向免疫系统提供了结构完整的表面，其中含有粘附素和脂多糖，并且与分离的蛋白质相比更稳定。我们希望优化幽门螺杆菌菌鬼，使其成为无需额外粘膜佐剂的有效疫苗。如果需要进一步的粘膜佐剂，则会产生重组菌影，在表面表达解毒版本的 CT 或耶尔森氏菌入侵素，以刺激或调节免疫系统。