Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.
Angiotensin-Converting Enzyme 2
/ metabolism
Animals
Antibodies, Monoclonal
/ genetics
Antibodies, Viral
/ genetics
Antibody Affinity
Betacoronavirus
/ immunology
Binding Sites
Binding Sites, Antibody
Broadly Neutralizing Antibodies
/ genetics
COVID-19
/ prevention & control
Cell Surface Display Techniques
Directed Molecular Evolution
Epitopes
/ immunology
Humans
Immunization, Passive
Immunoglobulin Fc Fragments
/ immunology
Mice, Inbred BALB C
Protein Domains
Protein Engineering
Receptors, Coronavirus
/ metabolism
Severe acute respiratory syndrome-related coronavirus
/ immunology
SARS-CoV-2
/ immunology
Severe Acute Respiratory Syndrome
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
COVID-19 Serotherapy
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
19 02 2021
19 02 2021
Historique:
received:
30
10
2020
accepted:
19
01
2021
pubmed:
27
1
2021
medline:
26
2
2021
entrez:
26
1
2021
Statut:
ppublish
Résumé
The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.
Identifiants
pubmed: 33495307
pii: science.abf4830
doi: 10.1126/science.abf4830
pmc: PMC7963221
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
Epitopes
0
Immunoglobulin Fc Fragments
0
Receptors, Coronavirus
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
823-829Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132317
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI157155
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073148
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127521
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132178
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142777
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA260543
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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