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Toxins 2011, 3(8), 979-990; doi:10.3390/toxins3080979

Mechanism of Lethal Toxin Neutralization by a Human Monoclonal Antibody Specific for the PA20 Region of Bacillus anthracis Protective Antigen

Children’s Hospital Oakland Research Institute, Oakland, CA 94609, USA
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Received: 29 April 2011 / Revised: 7 July 2011 / Accepted: 4 August 2011 / Published: 9 August 2011
(This article belongs to the Special Issue Anthrax Toxin)
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Abstract

The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA20) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the 166RKKR169 furin recognition sequence in domain 1 of PA. View Full-Text
Keywords: anthrax; Bacillus anthracis; antibody epitope; paratope; human monoclonal antibody; protective antigen; furin; toxin neutralization anthrax; Bacillus anthracis; antibody epitope; paratope; human monoclonal antibody; protective antigen; furin; toxin neutralization
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Reason, D.; Liberato, J.; Sun, J.; Camacho, J.; Zhou, J. Mechanism of Lethal Toxin Neutralization by a Human Monoclonal Antibody Specific for the PA20 Region of Bacillus anthracis Protective Antigen. Toxins 2011, 3, 979-990.

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