A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT/G Toxin in Mice.
Toxins (Basel)
; 15(5)2023 04 30.
Article
em En
| MEDLINE
| ID: mdl-37235351
ABSTRACT
Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® 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 KD values ranging from 3.86 nM to 103 nM (median KD 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 KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Botulismo
/
Antitoxinas
/
Toxinas Botulínicas Tipo A
/
Anticorpos de Cadeia Única
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article