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1 March 2006

Volume 193, Number 5
The Journal of Infectious Diseases 2006;193:625–633
0022-1899/2006/19305-0003
DOI: 10.1086/500148
MAJOR ARTICLE

Efficient Neutralization of Anthrax Toxin by Chimpanzee Monoclonal Antibodies against Protective Antigen

Zhaochun Chen,1

Mahtab Moayeri,3

Yi‐Hua Zhou,1

Stephen Leppla,3

Suzanne Emerson,2

Andrew Sebrell,1

Fujuan Yu,1

Juraj Svitel,4

Peter Schuck,4

Marisa St. Claire,5 and

Robert Purcell1

1Hepatitis Viruses Section and 2Molecular Hepatitis Section, Laboratory of Infectious Diseases, and 3Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, and 4Protein Biophysics Resource, National Institutes of Health, Bethesda, and 5Bioqual, Rockville, Maryland

Four single‐chain variable fragments (scFvs) against protective antigen (PA) and 2 scFvs against lethal factor (LF) of anthrax were isolated from a phage display library generated from immunized chimpanzees. Only 2 scFvs recognizing PA (W1 and W2) neutralized the cytotoxicity of lethal toxin in a macrophage lysis assay. Full‐length immunoglobulin G (IgG) of W1 and W2 efficiently protected rats from anthrax toxin challenge. The epitope recognized by W1 and W2 was conformational and was formed by C‐terminal amino acids 614–735 of PA. W1 and W2 each bound to PA with an equilibrium dissociation constant of mol/L to 5×10−11 mol/L, which is an affinity that is 20–100‐fold higher than that for the interaction of the receptor and PA. W1 and W2 inhibited the binding of PA to the receptor, suggesting that this was the mechanism of protection. These data suggest that W1 and W2 chimpanzee monoclonal antibodies may serve as PA entry inhibitors for use in the emergency prophylaxis against and treatment of anthrax.

Received 15 July 2005; accepted 20 September 2005; electronically published 2 February 2006.

Reprints or correspondence: Dr. Zhaochun Chen, Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 50, Rm. 6533, 50 South Dr., Bethesda, MD 20892 ().

Cited by

Momchilo Vuyisich, S. Gnanakaran, Julie A. Lovchik, C. Rick Lyons, Goutam Gupta. (2008) A Dual-Purpose Protein Ligand for Effective Therapy and Sensitive Diagnosis of Anthrax. The Protein Journal 27:5, 292-302
Online publication date: 1-Sep-2008.
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Sean V. Shadomy, Theresa L. Smith. (2008) Anthrax. Journal of the American Veterinary Medical Association 233:1, 63-72
Online publication date: 1-Aug-2008.
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Laura M Zarebski, Kerrie Vaughan, John Sidney, Bjoern Peters, Howard Grey, Kim D Janda, Arturo Casadevall, Alessandro Sette. (2008) Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum . Expert Review of Vaccines 7:1, 55-74
Online publication date: 1-Mar-2008.
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Dimitrios G Bouzianas. (2007) Potential biological targets of Bacillus anthracis in anti-infective approaches against the threat of bioterrorism. Expert Review of Anti-infective Therapy 5:4, 665-684
Online publication date: 1-Sep-2007.
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Yan Li, Kevin Sherer, Xizhong Cui, Peter Q Eichacker. (2007) New insights into the pathogenesis and treatment of anthrax toxin-induced shock. Expert Opinion on Biological Therapy 7:6, 843-854
Online publication date: 1-Jul-2007.
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Wendy A Keitel. (2006) Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine. Expert Review of Vaccines 5:4, 417-430
Online publication date: 1-Sep-2006.
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  • Potential conflicts of interest: none reported.

    Financial support: Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); NIH (contract no. N01‐AO‐02733).

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