title: A viral nanoparticle with dual function as an anthrax antitoxin and vaccine.
abstract: The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA) and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs) correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Darly J
authors.initials: DJ
authors.lastname: Manayani
authors.forename: Diane
authors.initials: D
authors.lastname: Thomas
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Dryden
authors.forename: Vijay
authors.initials: V
authors.lastname: Reddy
authors.forename: Marc E
authors.initials: ME
authors.lastname: Siladi
authors.forename: John M
authors.initials: JM
authors.lastname: Marlett
authors.forename: G Jonah A
authors.initials: GJ
authors.lastname: Rainey
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pique
authors.forename: Heather M
authors.initials: HM
authors.lastname: Scobie
authors.forename: Mark
authors.initials: M
authors.lastname: Yeager
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
authors.forename: Anette
authors.initials: A
authors.lastname: Schneemann
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial / Q000276:immunology; D000992:Antitoxins / Q000737:chemistry* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology; D005822:Genetic Vectors; D007497:Iridoviridae / Q000737:chemistry / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008854:Microscopy, Electron; D053758:Nanoparticles; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D018000:Receptors, Peptide
chemical_list: C447150:ANTXR2 protein, human; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D036022:Capsid Proteins; D008565:Membrane Proteins; D018000:Receptors, Peptide; C030325:anthrax toxin