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