title: A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1.
abstract: Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. anthracis lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and 10F4. These MAbs did not compete for binding to PA, consistent with specificities for different epitopes. The MAbs were tested for their ability to protect a monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G, the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the binding of PA or lethal factor or the formation of the PA heptamer complex. However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection.
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rivera
authors.forename: Antonio
authors.initials: A
authors.lastname: Nakouzi
authors.forename: Nareen
authors.initials: N
authors.lastname: Abboud
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Revskaya
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: R John
authors.initials: RJ
authors.lastname: Collier
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D000939:Epitopes; C030325:anthrax toxin