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口服CTB-UreI-UreB多表位疫苗对BALB/c小鼠幽门螺杆菌感染的保护作用

Protection against Helicobacter pylori infection in BALB/c mice by oral administration of multi-epitope vaccine of CTB-UreI-UreB.

作者信息

Yang Jing, Dai Lv-xia, Pan Xing, Wang Hongren, Li Bei, Zhu Jie, Li Ming-yuan, Shi Xin-Li, Wang Bao-ning

机构信息

Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China Sichuan Vaccine Technology Co. Ltd, Chengdu, Sichuan 610041, People's Republic of China Department of Infectious Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, People's Republic of China.

Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China Experiment Teaching Center of Clinical Medicine, Chengdu College of Medicine, Chengdu, Sichuan 610500, People's Republic of China.

出版信息

Pathog Dis. 2015 Jul;73(5). doi: 10.1093/femspd/ftv026. Epub 2015 Apr 6.

DOI:10.1093/femspd/ftv026
PMID:25846576
Abstract

Chronic gastric infection by the Gram-negative bacterium Helicobacter pylori (H. pylori) is strongly associated with gastritis, gastric ulcer and the development of distal gastric carcinoma and gastric mucosal lymphoma in humans. Antibiotic treatment of H. pylori is becoming less effective because of increasing antibiotic resistance; other treatment approaches such as specifically targeted methods, etc. to destroy this organism would be beneficial. An epitope vaccine is a promising option for protection against H. pylori infection. In this study, a multi-epitope vaccine was constructed by linking cholera toxin B subunit (CTB), two antigenic fragments of H. pylori urease I subunit (UreI20-29, UreI98-107) and four antigenic fragments of H. pylori urease B subunit (UreB12-23, UreB229-251, UreB327-400, UreB515-561), resulting in the recombinant CTB-UreI-UreB (BIB). Its protective effect against H. pylori infection was evaluated in BALB/c mice. Significant protection against H. pylori challenge was achieved in BALB/c mice immunized with BIB (15/18, 83.3%), rIB plus rCTB (6/18, 33.3%) and rIB (2/18, 11.1%) separately, while no protective effect was found in the mice immunized with either adjuvant rCTB alone or PBS. The induction of significant protection against H. pylori is possibly mediated by specific serum IgA and mucosal sIgA antibodies, and a mixed Th1/Th2/Th17 cells response. This multi-epitope vaccine might be a promising vaccine candidate that helps to control H. pylori infection.

摘要

革兰氏阴性菌幽门螺杆菌(H. pylori)的慢性胃部感染与人类胃炎、胃溃疡以及远端胃癌和胃黏膜淋巴瘤的发生密切相关。由于抗生素耐药性增加,幽门螺杆菌的抗生素治疗效果越来越差;其他治疗方法,如特异性靶向方法等,对消灭这种病原体将是有益的。表位疫苗是预防幽门螺杆菌感染的一个有前景的选择。在本研究中,通过连接霍乱毒素B亚基(CTB)、幽门螺杆菌脲酶I亚基的两个抗原片段(UreI20 - 29、UreI98 - 107)和幽门螺杆菌脲酶B亚基的四个抗原片段(UreB12 - 23、UreB229 - 251、UreB327 - 400、UreB515 - 561)构建了一种多表位疫苗,得到重组CTB - UreI - UreB(BIB)。在BALB/c小鼠中评估了其对幽门螺杆菌感染的保护作用。分别用BIB(15/18,83.3%)、rIB加rCTB(6/18,33.3%)和rIB(2/18,11.1%)免疫的BALB/c小鼠对幽门螺杆菌攻击具有显著保护作用,而单独用佐剂rCTB或PBS免疫的小鼠未发现保护作用。对幽门螺杆菌的显著保护作用的诱导可能由特异性血清IgA和黏膜sIgA抗体以及混合的Th1/Th2/Th17细胞反应介导。这种多表位疫苗可能是一种有前景的疫苗候选物,有助于控制幽门螺杆菌感染。

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