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

Darly J. Manayani, Diane Thomas, Kelly A. Dryden, Vijay Reddy, Marc E. Siladi, John M. Marlett, G. Jonah A. Rainey, Michael E. Pique, Heather M. Scobie, Mark Yeager, John A.T. Young, Marianne Manchester, Anette Schneemann

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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 viruslike 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.

Original languageEnglish (US)
Pages (from-to)1422-1431
Number of pages10
JournalPLoS pathogens
Volume3
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

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