A viral nanoparticle with dual function as an anthrax antitoxin and vaccine.
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.
Manayani
Darly J
DJ
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Thomas
Diane
D
Dryden
Kelly A
KA
Reddy
Vijay
V
Siladi
Marc E
ME
Marlett
John M
JM
Rainey
G Jonah A
GJ
Pique
Michael E
ME
Scobie
Heather M
HM
Yeager
Mark
M
Young
John A T
JA
Manchester
Marianne
M
Schneemann
Anette
A
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
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