A highly potent antibody effective against SARS-CoV-2 variants of concern.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
B-Lymphocytes
/ immunology
Broadly Neutralizing Antibodies
/ immunology
COVID-19
/ immunology
Cell Line
Cricetinae
Disease Models, Animal
Epitopes
/ immunology
Humans
Immunoglobulin Fab Fragments
/ immunology
Neutralization Tests
Protein Binding
/ immunology
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
Structure-Activity Relationship
Vaccination
COVID-19 Drug Treatment
SARS-CoV-2
neutralizing antibodies
variants of concern
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 10 2021
12 10 2021
Historique:
received:
28
04
2021
revised:
09
07
2021
accepted:
17
09
2021
pubmed:
3
10
2021
medline:
3
11
2021
entrez:
2
10
2021
Statut:
ppublish
Résumé
Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.
Identifiants
pubmed: 34599871
pii: S2211-1247(21)01278-X
doi: 10.1016/j.celrep.2021.109814
pmc: PMC8452523
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
Epitopes
0
Immunoglobulin Fab Fragments
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109814Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.F., P.T., G.P., and D.T declare that they are co-inventors on a patent application titled “Neutralizing antibodies and use thereof in the treatment of SARS-CoV-2 infection” with filing number PCT/IB2021/050621 that covers newly identified antibodies described in this manuscript. The remaining authors declare no competing interests.
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