A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro

作者：Ding Guipeng; Chen Ximin; Zhu Jin; Due**ery Nicholas S; Cheng Xunjia; Cao Brian^*

来源：Clinical and Developmental Immunology, 2013, 2013: 475809.

DOI：10.1155/2013/475809

Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46x10(7) L/mol and could neutralize LeTx with an EC50 of 85 mu g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.

• 出版日期2013
• 单位南京医科大学; 复旦大学