A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal ToxinIn Vitro

Abstract

Human anthrax infection caused by exposure toBacillus anthraciscannot 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 inEscherichia colicould specifically identify LF with an affinity of3.46×107 L/mol and could neutralize LeTx with an EC50of 85 μg/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cellsin vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.