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PLoS Pathog. 2007 Oct 5;3(10):1422-31.

A viral nanoparticle with dual function as an anthrax antitoxin and vaccine.

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1
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

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.

PMID:
17922572
PMCID:
PMC2000967
DOI:
10.1371/journal.ppat.0030142
[Indexed for MEDLINE]
Free PMC Article
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