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





