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: Zhaochun Chen, Mahtab Moayeri, Huaying Zhao, Devorah Crown, Stephen H Leppla, Robert H Purcell
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 32 Pg. 13487-92 (Aug 11 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19651602 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Antigens, Bacterial
• Bacterial Toxins
• Calmodulin
• Immunoglobulin Fab Fragments
• anthrax toxin

Topics

• Animals
• Antibodies, Monoclonal (immunology, isolation & purification)
• Antibody Affinity
• Antigens, Bacterial (chemistry, immunology)
• Bacterial Toxins (chemistry, immunology)
• Binding, Competitive
• Calmodulin (metabolism)
• Edema (chemically induced, immunology, prevention & control)
• Humans
• Immunoglobulin Fab Fragments (immunology)
• Mice
• Neutralization Tests
• Pan troglodytes (immunology)
• Protein Binding
• Protein Structure, Tertiary
• Ultracentrifugation