title: Mouse monoclonal antibodies to anthrax edema factor protect against infection.
abstract: Bacillus anthracis is the causative agent of anthrax, and the tripartite anthrax toxin is an essential element of its pathogenesis. Edema factor (EF), a potent adenylyl cyclase, is one of the toxin components. In this work, anti-EF monoclonal antibodies (MAb) were produced following immunization of mice, and four of the antibodies were fully characterized. MAb 3F2 has an affinity of 388 pM, was most effective for EF detection, and appears to be the first antibody reported to neutralize EF by binding to the catalytic C(B) domain. MAb 7F10 shows potent neutralization of edema toxin activity in vitro and in vivo; it targets the N-terminal protective antigen binding domain. The four MAb react with three different domains of edema factor, and all were able to detect purified edema factor in Western blot analysis. None of the four MAb cross-reacted with the lethal factor toxin component. Three of the four MAb protected mice in both a systemic edema toxin challenge model and a subcutaneous spore-induced foreleg edema model. A combination of three of the MAb also significantly delayed the time to death in a third subcutaneous spore challenge model. This appears to be the first direct evidence that monoclonal antibody-mediated neutralization of EF alone is sufficient to delay anthrax disease progression.
authors.affiliation: Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 33/Room 1W20B.7, Bethesda, MD 20892-3202, USA.
authors.forename: Clinton E
authors.initials: CE
authors.lastname: Leysath
authors.forename: Kuang-Hua
authors.initials: KH
authors.lastname: Chen
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.forename: Devorah
authors.initials: D
authors.lastname: Crown
authors.forename: Rasem
authors.initials: R
authors.lastname: Fattah
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Chen
authors.forename: Suman R
authors.initials: SR
authors.lastname: Das
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity; D001427:Bacterial Toxins / Q000276:immunology* / Q000633:toxicity; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006825:Hybridomas; D007114:Immunization; D007074:Immunoglobulin G; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D022122:Anthrax Vaccines; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007074:Immunoglobulin G; C030325:anthrax toxin