Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding

Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13487-92. doi: 10.1073/pnas.0906581106. Epub 2009 Jul 27.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

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

Substances

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