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