# Chimeric Antibody Engineering Against Bacillus anthracis Lethal Toxin: Neutralization Efficacy and Mechanism of Action

## TL;DR

Scientists engineered a chimeric antibody that neutralizes a deadly toxin from Bacillus anthracis by blocking its entry into cells, offering a potential treatment for late-stage anthrax.

## Contribution

A novel chimeric monoclonal antibody (xi1E10) was developed and shown to neutralize anthrax lethal toxin by inhibiting pore formation.

## Key findings

- The chimeric antibody xi1E10 neutralizes lethal toxin both in vitro and in vivo.
- xi1E10 suppresses functional pore formation, blocking lethal factor translocation into the cytosol.
- The antibody shows promise as a therapeutic candidate for late-stage anthrax treatment.

## Abstract

Bacillus anthracis has three main virulence factors: an extracellular capsule and two binary toxins (lethal toxin—consists of a lethal factor and a protective antigen, and edema toxin—consists of an edema factor and a protective antigen). In the Russian Federation, the epidemiological situation regarding anthrax infection remains unfavorable. In the late stages of an anthrax infection, antibiotic therapy becomes ineffective and the patient dies within 24 h as a large amount of lethal toxin accumulates in the patient’s blood. Antibodies capable of neutralising lethal toxin (LT) can be an effective treatment for these patients. The objective of the study was to construct a chimeric monoclonal antibody targeting the protective antigen of the LT and to elucidate its mechanism of toxin neutralization. In this work, a chimeric monoclonal antibody (xi1E10) directed against the protective antigen was successfully produced. Both in vitro and in vivo experiments demonstrated the capacity of xi1E10 to neutralize lethal toxin. Confocal microscopy revealed that xi1E10 effectively suppresses the formation of a functional pore, thereby blocking the translocation of the lethal factor into the cytosol. These findings indicate that the monoclonal antibody xi1E10 represents a promising candidate for the development of a therapeutic drug.