title: Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding.
abstract: This study describes the isolation and characterization of a neutralizing monoclonal antibody (mAb) against anthrax edema factor, EF13D. EF13D neutralized edema toxin (ET)-mediated cyclic AMP (cAMP) responses in cells and protected mice from both ET-induced footpad edema and systemic ET-mediated lethality. The antibody epitope was mapped to domain IV of EF. The mAb was able to compete with calmodulin (CaM) for EF binding and displaced CaM from EF-CaM complexes. EF-mAb binding affinity (0.05-0.12 nM) was 50- to 130-fold higher than that reported for EF-CaM. This anti-EF neutralizing mAb could potentially be used alone or with an anti-PA mAb in the emergency prophylaxis and treatment of anthrax infection.
authors: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. zchen@niaid.nih.gov
authors: Zhaochun
authors: Z
authors: Chen
authors: Mahtab
authors: M
authors: Moayeri
authors: Huaying
authors: H
authors: Zhao
authors: Devorah
authors: D
authors: Crown
authors: Stephen H
authors: SH
authors: Leppla
authors: Robert H
authors: RH
authors: Purcell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology*; D001667:Binding, Competitive; D002147:Calmodulin / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D002679:Pan troglodytes / Q000276:immunology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014461:Ultracentrifugation
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002147:Calmodulin; D007140:Immunoglobulin Fab Fragments; C030325:anthrax toxin