A Monoclonal Antibody to Bacillus Anthracis Protective Antigen Defines a Neutralizing Epitope in Domain 1

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2006 Jun 23

PMID 16790789

Citations 32

Authors

Johanna Rivera

Antonio Nakouzi

Nareen Abboud

Ekaterina Revskaya

David Goldman

R John Collier

Ekaterina Dadachova

Arturo Casadevall

Affiliations

Soon will be listed here.

Abstract

Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. anthracis lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and 10F4. These MAbs did not compete for binding to PA, consistent with specificities for different epitopes. The MAbs were tested for their ability to protect a monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G, the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the binding of PA or lethal factor or the formation of the PA heptamer complex. However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection.

Citing Articles

Binding of the von Willebrand Factor A Domain of Capillary Morphogenesis Protein 2 to Anthrax Protective Antigen Vaccine Reduces Immunogenicity in Mice.

de Oliveira F, Mamillapalli S, Gonti S, Brey R, Li H, Schiffer J mSphere. 2020; 5(1).

PMID: 31941807 PMC: 6968648. DOI: 10.1128/mSphere.00556-19.

Serum-Mediated Cleavage of Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase.

Goldman D, Nieves E, Nakouzi A, Rivera J, Phyu E, Win T mSphere. 2018; 3(3).

PMID: 29950379 PMC: 6021598. DOI: 10.1128/mSphere.00091-18.

Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge.

Devera T, Prusator D, Joshi S, Ballard J, Lang M Toxins (Basel). 2015; 7(7):2371-84.

PMID: 26120785 PMC: 4516918. DOI: 10.3390/toxins7072371.

Identification of peptide sequences as a measure of Anthrax vaccine stability during storage.

Whiting G, Wheeler J, Rijpkema S Hum Vaccin Immunother. 2014; 10(6):1669-81.

PMID: 24637775 PMC: 4185962. DOI: 10.4161/hv.28443.

Platelet-activating factor contributes to Bacillus anthracis lethal toxin-associated damage.

Rivera J, Sellers R, Zeng W, van Rooijen N, Casadevall A, Goldman D J Biol Chem. 2014; 289(10):7131-7141.

PMID: 24478317 PMC: 3945373. DOI: 10.1074/jbc.M113.524900.

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