Open AccessToxin-neutralizing antibodies elicited by naturally acquired cutaneous anthrax are elevated following severe disease and appear to target conformational epitopes
Author(s) -
Eric K. Dumas,
Hayati Demiraslan,
Rebecca J. Ingram,
Rebecca M Sparks,
Emily E. Muns,
Adriana Zamora,
Jason L. Larabee,
Lori Garman,
Jimmy D. Ballard,
GeertJan Boons,
Judith A. James,
Üner Kayabaş,
Mehmet Doğanay,
A. Darise Farris
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0230782
Subject(s) - anthrax toxin , bacillus anthracis , anthrax vaccines , epitope , antigen , antibody , immune system , toxin , microbiology and biotechnology , conformational epitope , biology , vaccination , virology , immunology , immunization , fusion protein , biochemistry , bacteria , dna vaccination , genetics , gene , recombinant dna
Understanding immune responses to native antigens in response to natural infections can lead to improved approaches to vaccination. This study sought to characterize the humoral immune response to anthrax toxin components, capsule and spore antigens in individuals (n = 46) from the Kayseri and Malatya regions of Turkey who had recovered from mild or severe forms of cutaneous anthrax infection, compared to regional healthy controls (n = 20). IgG antibodies to each toxin component, the poly-γ-D-glutamic acid capsule, the Bacillus collagen-like protein of anthracis (BclA) spore antigen, and the spore carbohydrate anthrose, were detected in the cases, with anthrax toxin neutralization and responses to Protective Antigen (PA) and Lethal Factor (LF) being higher following severe forms of the disease. Significant correlative relationships among responses to PA, LF, Edema Factor (EF) and capsule were observed among the cases. Though some regional control sera exhibited binding to a subset of the tested antigens, these samples did not neutralize anthrax toxins and lacked correlative relationships among antigen binding specificities observed in the cases. Comparison of serum binding to overlapping decapeptides covering the entire length of PA, LF and EF proteins in 26 cases compared to 8 regional controls revealed that anthrax toxin-neutralizing antibody responses elicited following natural cutaneous anthrax infection are directed to conformational epitopes. These studies support the concept of vaccination approaches that preserve conformational epitopes.