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Camelid VHH Antibodies that Neutralize Botulinum Neurotoxin Serotype E Intoxication or Protease Function

Authors :
Jacqueline M. Tremblay
Edwin Vazquez-Cintron
Kwok-Ho Lam
Jean Mukherjee
Daniela Bedenice
Celinia A. Ondeck
Matthieu T. Conroy
Skylar M. L. Bodt
Brittany M. Winner
Robert P. Webb
Konstantin Ichtchenko
Rongsheng Jin
Patrick M. McNutt
Charles B. Shoemaker
Source :
Toxins, Vol 12, Iss 10, p 611 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Botulinum neurotoxin (BoNT) serotype E is one of three serotypes that cause the preponderance of human botulism cases and is a Tier 1 Select Agent. BoNT/E is unusual among BoNT serotypes for its rapid onset and short duration of intoxication. Here we report two large panels of unique, unrelated camelid single-domain antibodies (VHHs) that were selected for their ability to bind to BoNT/E holotoxin and/or to the BoNT/E light chain protease domain (LC/E). The 19 VHHs which bind to BoNT/E were characterized for their subunit specificity and 8 VHHs displayed the ability to neutralize BoNT/E intoxication of neurons. Heterodimer antitoxins consisting of two BoNT/E-neutralizing VHHs, including one heterodimer designed using structural information for simultaneous binding, were shown to protect mice against co-administered toxin challenges of up to 500 MIPLD50. The 22 unique VHHs which bind to LC/E were characterized for their binding properties and 9 displayed the ability to inhibit LC/E protease activity. Surprisingly, VHHs selected on plastic-coated LC/E were virtually unable to recognize soluble or captured LC/E while VHHs selected on captured LC/E were poorly able to recognize LC/E coated to a plastic surface. This panel of anti-LC/E VHHs offer insight into BoNT/E function, and some may have value as components of therapeutic antidotes that reverse paralysis following BoNT/E exposures.

Details

Language :
English
ISSN :
20726651
Volume :
12
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
edsdoj.0c70bccd9e4043258a5d427728aa1493
Document Type :
article
Full Text :
https://doi.org/10.3390/toxins12100611