title: The early humoral immune response to Bacillus anthracis toxins in patients infected with cutaneous anthrax.
abstract: Bacillus anthracis, the causative agent of anthrax, produces a tripartite toxin composed of two enzymatically active subunits, lethal factor (LF) and edema factor (EF), which, when associated with a cell-binding component, protective antigen (PA), form lethal toxin and edema toxin, respectively. In this preliminary study, we characterized the toxin-specific antibody responses observed in 17 individuals infected with cutaneous anthrax. The majority of the toxin-specific antibody responses observed following infection were directed against LF, with immunoglobulin G (IgG) detected as early as 4 days after the onset of symptoms in contrast to the later and lower EF- and PA-specific IgG responses. Unlike the case with infection, the predominant toxin-specific antibody response of those immunized with the US anthrax vaccine absorbed and UK anthrax vaccine precipitated licensed anthrax vaccines was directed against PA. We observed that the LF-specific human antibodies were, like anti-PA antibodies, able to neutralize toxin activity, suggesting the possibility that they may contribute to protection. We conclude that an antibody response to LF might be a more sensitive diagnostic marker of anthrax than to PA. The ability of human LF-specific antibodies to neutralize toxin activity supports the possible inclusion of LF in future anthrax vaccines.
authors.affiliation: Biological Defense Research Directorate, Naval Medical Research Center, Rockville, MD, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Brenneman
authors.forename: Mehmet
authors.initials: M
authors.lastname: Doganay
authors.forename: Arya
authors.initials: A
authors.lastname: Akmal
authors.forename: Stanley
authors.initials: S
authors.lastname: Goldman
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Galloway
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Mateczun
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Baillie
mesh_terms: D000881:Anthrax / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood*; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins / Q000097:blood*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D017192:Skin Diseases, Bacterial
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D007074:Immunoglobulin G; C030325:anthrax toxin