Development of a human antibody fragment cross-neutralizing scorpion toxins.
Cross-neutralization
Cross-reactivity
Directed evolution
Human scFv
Phage display
Scorpion toxins
Journal
Molecular immunology
ISSN: 1872-9142
Titre abrégé: Mol Immunol
Pays: England
ID NLM: 7905289
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
18
11
2022
revised:
07
02
2023
accepted:
15
02
2023
pubmed:
23
2
2023
medline:
7
3
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Previously, it was demonstrated that from the single chain fragment variable (scFv) 3F it is possible to generate variants capable of neutralizing the Cn2 and Css2 toxins, as well as their respective venoms (Centruroides noxius and Centruroides suffusus). Despite this success, it has not been easy to modify the recognition of this family of scFvs toward other dangerous scorpion toxins. The analysis of toxin-scFv interactions and in vitro maturation strategies allowed us to propose a new maturation pathway for scFv 3F to broaden recognition toward other Mexican scorpion toxins. From maturation processes against toxins CeII9 from C. elegans and Ct1a from C. tecomanus, the scFv RAS27 was developed. This scFv showed an increased affinity and cross-reactivity for at least 9 different toxins while maintaining recognition for its original target, the Cn2 toxin. In addition, it was confirmed that it can neutralize at least three different toxins. These results constitute an important advance since it was possible to improve the cross-reactivity and neutralizing capacity of the scFv 3F family of antibodies.
Identifiants
pubmed: 36812764
pii: S0161-5890(23)00028-7
doi: 10.1016/j.molimm.2023.02.006
pii:
doi:
Substances chimiques
Scorpion Venoms
0
Antibodies, Neutralizing
0
Immunoglobulin Fragments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165-174Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest The authors declare no conflict of interest.