A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine

PLoS Pathogens

Diane Thomas¹  Kelly A Dryden¹  John A. T Young¹  Darly J Manayani²  Michael E Pique²  Mark Yeager²  Vijay Reddy²  Marc E Siladi²  Marianne Manchester³  G. Jonah A Rainey⁴  Anette Schneemann⁴  John M Marlett⁴  Heather M Scobie⁴ 

[1] Department of Cell Biology, The Scripps Research Institute, La Jolla, California , United States of America;Department of Molecular Biology, The Scripps Research Institute, La Jolla, California , United States of America;Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, California, United States of America;The Salk Institute for Biological Studies, La Jolla, California, United States of America

关键词: Anthrax;    Toxins;    Antibody response;    Intoxication;    Antibodies;    Vaccines;    Antitoxins;    Vaccine development;   

DOI  :  10.1371/journal.ppat.0030142

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY