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A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT/G Toxin in Mice.

Authors :
Fan, Yongfeng
Lou, Jianlong
Tam, Christina C.
Wen, Weihua
Conrad, Fraser
Leal da Silva Alves, Priscila
Cheng, Luisa W.
Garcia-Rodriguez, Consuelo
Farr-Jones, Shauna
Marks, James D.
Source :
Toxins; May2023, Vol. 15 Issue 5, p316, 16p
Publication Year :
2023

Abstract

Equine-derived antitoxin (BAT<superscript>®</superscript>) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT<superscript>®</superscript> is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with K<subscript>D</subscript> values ranging from 3.86 nM to 103 nM (median K<subscript>D</subscript> 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG K<subscript>D</subscript> values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD<subscript>50</subscript>s of BoNT/G at a total mAb dose of 6.25 μg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726651
Volume :
15
Issue :
5
Database :
Complementary Index
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
163984186
Full Text :
https://doi.org/10.3390/toxins15050316