African Journal of
Microbiology Research

  • Abbreviation: Afr. J. Microbiol. Res.
  • Language: English
  • ISSN: 1996-0808
  • DOI: 10.5897/AJMR
  • Start Year: 2007
  • Published Articles: 5233

Full Length Research Paper

Engineering and evaluation of a mouse/human chimeric antibody against Shiga toxin 2

Li Zhang1#, Yongjun Jiao1#, Qiu Jin2#, Lin Bao3, Xiaoyan Zeng1, Xiling Guo1, Xian Qi1, Mingming Huang4, Tao Wu1, Yin Chen1, Zhenqing Feng2, and Zhiyang Shi1*   #Li Zhang, Yongjun Jiao and Qiu Jin contributed equally to this paper.
1Key Laboratory of Enteric Pathogenic Microbiology, Ministry of Health, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210009, China. 2Key Laboratory of Antibody Technology, Ministry of Health, Nanjing Medical University, Nanjing 210029, China. 3School of Public Health, Nanjing Medical University, Nanjing 210029, China. 4School of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Email: [email protected]

  •  Accepted: 27 November 2012
  •  Published: 01 January 2013

Abstract

Hemolytic-uremic syndrome (HUS), mainly caused by Shiga toxin (Stx) producingEscherichia coli (STEC) such as E. coli O157:H7 and STEC/EAggEC, is a serious complication predominantly leading to renal failure and even death. We have previously reported that a monoclonal antibody effectively neutralizes Stx2 in vitro and in vivo toxicity models. As a therapeutic agent against HUS, the mouse origin of this antibody can trigger human anti-murine antibody (HAMA) reactions thereby restricting its clinical application. In order to reduce its immunogenicity for use in humans, in this study, a mouse/human chimeric antibody designated rS2C4-IgG1 was developed in baculovirus/insect cell expression system. Analysis of antigen-binding and competitive binding revealed that rS2C4-IgG1 possessed specificity and affinity similar to that of S2C4. Results from cytotoxicity assays and mouse toxicity model analysis showed that rS2C4-IgG1offers neutralizing activity comparable to its parent MAb in vitro and in vivo. Therefore, the chimeric rS2C4-IgG1 had great potential for use in the treatment of STEC infection.

 

Key words: Shiga toxin 2, HUS, STEC, chimeric rS2C4-IgG1.