Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity.
Antibodies, Neutralizing
/ chemistry
Antibody Affinity
/ immunology
Broadly Neutralizing Antibodies
/ chemistry
Epitopes
/ chemistry
HIV Antibodies
/ chemistry
HIV-1
/ immunology
Humans
Models, Molecular
Neutralization Tests
/ methods
Protein Conformation
Protein Engineering
/ methods
Structure-Activity Relationship
HIV-1
antibody
neutralization
protein engineering
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
25 01 2022
25 01 2022
Historique:
accepted:
15
12
2021
entrez:
22
1
2022
pubmed:
23
1
2022
medline:
1
3
2022
Statut:
ppublish
Résumé
Deep mining of B cell repertoires of HIV-1-infected individuals has resulted in the isolation of dozens of HIV-1 broadly neutralizing antibodies (bNAbs). Yet, it remains uncertain whether any such bNAbs alone are sufficiently broad and potent to deploy therapeutically. Here, we engineered HIV-1 bNAbs for their combination on a single multispecific and avid molecule via direct genetic fusion of their Fab fragments to the human apoferritin light chain. The resulting molecule demonstrated a remarkable median IC
Identifiants
pubmed: 35064083
pii: 2112887119
doi: 10.1073/pnas.2112887119
pmc: PMC8795538
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
Epitopes
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2022 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: The Hospital for Sick Children has applied for patents concerning the Multabody platform technology that are related to this work. B.T. and J.-P.J. are founders of Radiant Biotherapeutics and are members of its Scientific Advisory Board.
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