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

Toxins

Donald Reason¹  Justine Liberato²  Jinying Sun²  Jessica Camacho² 

[1] Children’s Hospital Oakland Research Institute, Oakland, CA 94609, USA;

关键词: anthrax;    Bacillus anthracis;    antibody epitope;    paratope;    human monoclonal antibody;    protective antigen;    furin;    toxin neutralization;   

DOI  :  10.3390/toxins3080979

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.