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Infection and Immunity, July 2006, p. 4149-4156, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00150-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Johanna Rivera,3 Antonio Nakouzi,3 Nareen Abboud,1 Ekaterina Revskaya,2 David Goldman,4 R. John Collier,5 Ekaterina Dadachova,1,2 and Arturo Casadevall1,3*

Department of Microbiology and Immunology,1 Department of Nuclear Medicine,2 Department of Medicine, Division of Infectious Diseases,3 Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461,4 Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 021155

Received 30 January 2006/ Returned for modification 13 March 2006/ Accepted 9 April 2006

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.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-3730. Fax: (718) 430-8968. E-mail: casadeva{at}aecom.yu.edu.

Editor: J. T. Barbieri

Infection and Immunity, July 2006, p. 4149-4156, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00150-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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