Engineering an anti-Stx2 antibody to control severe infections of EHEC O157:H7

被引:20
作者
Ma, Ying [2 ,3 ]
Mao, Xuhu [2 ]
Li, Jun [1 ]
Li, Haixia [2 ]
Feng, Youjun [3 ]
Chen, Hongzhang [2 ]
Luo, Ping [2 ]
Gu, Jiang [2 ]
Yu, Shu [2 ]
Zeng, Hao [2 ]
Guo, Gang [2 ]
Yang, Kang [1 ]
Zou, Quanming [2 ]
机构
[1] Third Mil Med Univ, Southwest Hosp, Dept Cardiothorac Surg, Chongqing 400038, Peoples R China
[2] Third Mil Med Univ, Coll Med Lab, Dept Clin Microbiol & Clin Immunol, Chongqing 400038, Peoples R China
[3] Chinese Acad Sci, Inst Microbiol, Ctr Mol Immunol, Beijing 100010, Peoples R China
基金
中国国家自然科学基金;
关键词
EHEC O157:H7; Shiga toxin 2 (Stx2); scFv;
D O I
10.1016/j.imlet.2008.09.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7, a primary enteric pathogen, has been implicated in a wide spectrum of food/water-borne infectious diseases such as hemorrhagic colitis (HC) and hemolyticuremic syndrome (HUS). Effective treatments for EHEC O157:H7 induced disease are not available yet. Shiga-toxin 2 (Stx2) has been related to clinical manifestations of HUS, suggesting its critical role in pathology following infection with EHEC O157: H7. Here we report the development of four anti-Stx2-Monoclonal antibodies (McAbs) (5F3 and 5C11 for Stx2A, and 1A4 and 1A5 for Stx2B), all of which have strong immunogenicity and neutralization activities in vitro and in vivo. The full-length cDNA coding for anti-Stx2A McAb, 5F3, was cloned and an engineered antibody was developed whose therapeutic effects were evaluated. Our data indicate that the engineered scFv together with two new McAbs may be applicable for the prevention and therapy of EHEC induced pathology. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:110 / 115
页数:6
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