Efficient neutralization of antibody-resistant forms of anthrax toxin by a soluble receptor decoy inhibitor.
A soluble receptor decoy inhibitor (RDI), comprised of the extracellular I domain of ANTXR2, is a candidate anthrax therapeutic. Here we show that RDI can effectively neutralize altered forms of the protective antigen toxin subunit that are resistant to 14B7 monoclonal antibody neutralization. These data highlight the potential of RDI to act as an adjunct to existing antibody-based therapies and indicate that inhibitors based on RDI might be useful as a stand-alone treatment against specifically engineered strains of Bacillus anthracis.
Sharma
Shilpi
S
The Salk Institute for Biological Studies, Infectious Disease Laboratory, La Jolla, California 92037, USA.
Thomas
Diane
D
Marlett
John
J
Manchester
Marianne
M
Young
John A T
JA
D000818:Animals; D000881:Anthrax / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001427:Bacterial Toxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007700:Kinetics; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008970:Molecular Weight; D009154:Mutation; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D018000:Receptors, Peptide / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors