title: Immunisation with anthrolysin O or a genetic toxoid protects against challenge with the toxin but not against Bacillus anthracis.
abstract: Anthrolysin O (ALO) is a toxin produced by Bacillus anthracis, the causative agent of anthrax. It is a member of the cholesterol-dependent cytolysin (CDC) group of toxins, many of which are potential vaccine candidates that protect against their producing organisms. Pore formation by ALO was studied by transmission electron microscopy and pores were found to be consistent with those formed by other members of this toxin family. We constructed and characterised a novel genetic toxoid of anthrolysin O, Delta6mALO, which was able to bind to cells but was incapable of pore-formation or haemolysis. The capacity of the haemolytic and non-haemolytic forms of ALO to protect against challenge with the toxin or B. anthracis was determined. Immunisation with both active and non-haemolytic forms of ALO elicited protection against lethal i.v. challenge with ALO but neither was protective against B. anthracis in a murine i.p. challenge model. Immunisation with another CDC, pneumolysin, did not confer cross-protection against challenge with ALO. Histopathological investigation following lethal i.v. challenge with ALO revealed acute pathology in the lungs with occlusion of alveolar vessels by fibrin deposits.
authors.affiliation: Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Graeme J M
authors.initials: GJ
authors.lastname: Cowan
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
authors.forename: Linda K
authors.initials: LK
authors.lastname: Johnson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D000942:Antigens, Bacterial / Q000633:toxicity*; D000992:Antitoxins / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006461:Hemolysis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011041:Poisoning / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D014121:Toxoids / Q000235:genetics / Q000276:immunology* / Q000633:toxicity
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014121:Toxoids; C030325:anthrax toxin; C498000:anthrolysin O, Bacillus anthracis