Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Viral
/ immunology
Broadly Neutralizing Antibodies
/ immunology
COVID-19
/ immunology
Cells, Cultured
Chlorocebus aethiops
Cross Reactions
/ immunology
Female
HEK293 Cells
Humans
Male
Middle Aged
Neutralization Tests
/ methods
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
Vero Cells
COVID-19
SARS-CoV-2
broadly neutralizing antibodies
cryo-EM
emerging variants
ultrapotent monoclonal antibodies
variants of concern
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
12 01 2022
12 01 2022
Historique:
received:
28
09
2021
revised:
08
11
2021
accepted:
10
12
2021
pubmed:
2
1
2022
medline:
27
1
2022
entrez:
1
1
2022
Statut:
ppublish
Résumé
A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both "up" and "down" conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.
Identifiants
pubmed: 34973165
pii: S1931-3128(21)00581-3
doi: 10.1016/j.chom.2021.12.010
pmc: PMC8683262
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
Spike Glycoprotein, Coronavirus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-82.e10Subventions
Organisme : NIAID NIH HHS
ID : P01 AI138938
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests F. Klein, K.V., and H.G. are listed as inventors on a patent application that covers aspects of this work. F.K., C.K., and H.G. are listed as inventors on a patent application regarding neutralizing antibodies against SARS-related coronaviruses. All other authors declare no competing interests.
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