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

PLoS Pathog. 2007 Oct 5;3(10):1422-31. doi: 10.1371/journal.ppat.0030142.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anthrax / prevention & control*
  • Anthrax Vaccines*
  • Antigens, Bacterial / immunology
  • Antitoxins / chemistry*
  • Antitoxins / metabolism*
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / immunology
  • Capsid Proteins / chemistry
  • Capsid Proteins / immunology
  • Genetic Vectors
  • Iridoviridae / chemistry
  • Iridoviridae / immunology
  • Male
  • Membrane Proteins / chemistry*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Nanoparticles
  • Polymerase Chain Reaction
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Peptide

Substances

  • ANTXR2 protein, human
  • Anthrax Vaccines
  • Antigens, Bacterial
  • Antitoxins
  • Bacterial Toxins
  • Capsid Proteins
  • Membrane Proteins
  • Receptors, Peptide
  • anthrax toxin