title: Mechanism of lethal toxin neutralization by a human monoclonal antibody specific for the PA(20) region of Bacillus anthracis protective antigen.
abstract: The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA(20)) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the (166)RKKR(169) furin recognition sequence in domain 1 of PA.
authors: Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. dreason@chori.org
authors: Donald
authors: D
authors: Reason
authors: Justine
authors: J
authors: Liberato
authors: Jinying
authors: J
authors: Sun
authors: Jessica
authors: J
authors: Camacho
authors: Jianhui
authors: J
authors: Zhou
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity; D000992:Antitoxins / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology* / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002460:Cell Line; D003001:Cloning, Molecular; D045683:Furin / Q000737:chemistry; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D011487:Protein Conformation
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; C030325:anthrax toxin; D045683:Furin