The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against viral variants.
Animals
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Neutralizing
/ administration & dosage
Antibody Affinity
COVID-19
/ therapy
Epitopes
/ genetics
Humans
Immunization, Passive
Mice
Mice, Transgenic
Models, Molecular
Neutralization Tests
Protein Domains
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ chemistry
Treatment Outcome
COVID-19 Serotherapy
K18-hACE2 mice
SARS-CoV-2
VOCs
escape mutants
mAbs
neutralizing antibodies
variants
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
07 09 2021
07 09 2021
Historique:
received:
17
03
2021
revised:
01
07
2021
accepted:
17
08
2021
pubmed:
1
9
2021
medline:
16
9
2021
entrez:
31
8
2021
Statut:
ppublish
Résumé
A wide range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing monoclonal antibodies (mAbs) have been reported, most of which target the spike glycoprotein. Therapeutic implementation of these antibodies has been challenged by emerging SARS-CoV-2 variants harboring mutated spike versions. Consequently, re-assessment of previously identified mAbs is of high priority. Four previously selected mAbs targeting non-overlapping epitopes are now evaluated for binding potency to mutated RBD versions, reported to mediate escape from antibody neutralization. In vitro neutralization potencies of these mAbs, and two NTD-specific mAbs, are evaluated against two frequent SARS-CoV-2 variants of concern, the B.1.1.7 Alpha and the B.1.351 Beta. Furthermore, we demonstrate therapeutic potential of three selected mAbs by treatment of K18-human angiotensin-converting enzyme 2 (hACE2) transgenic mice 2 days post-infection with each virus variant. Thus, despite the accumulation of spike mutations, the highly potent MD65 and BL6 mAbs retain their ability to bind the prevalent viral mutants, effectively protecting against B.1.1.7 and B.1.351 variants.
Identifiants
pubmed: 34464610
pii: S2211-1247(21)01123-2
doi: 10.1016/j.celrep.2021.109679
pmc: PMC8379094
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Epitopes
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
109679Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Patent application for the described antibodies was filed by the Israel Institute for Biological Research. None of the authors declared any additional competing interests.
Références
Signal Transduct Target Ther. 2020 Aug 25;5(1):170
pubmed: 32843617
Anal Bioanal Chem. 2021 May;413(13):3501-3510
pubmed: 33768365
Cell. 2020 Dec 10;183(6):1735
pubmed: 33306958
Stem Cell Res. 2020 Dec 15;50:102125
pubmed: 33341604
Cell. 2021 Mar 4;184(5):1171-1187.e20
pubmed: 33621484
Cell Mol Immunol. 2021 Apr;18(4):1061-1063
pubmed: 33633321
Nature. 2020 Oct;586(7830):516-527
pubmed: 32967006
Nature. 2021 Apr;592(7853):277-282
pubmed: 33545711
Cell. 2020 Aug 20;182(4):828-842.e16
pubmed: 32645326
Nature. 2021 May;593(7857):130-135
pubmed: 33684923
Cell. 2021 May 27;184(11):2939-2954.e9
pubmed: 33852911
Science. 2020 Aug 28;369(6507):1119-1123
pubmed: 32661058
Elife. 2020 Oct 28;9:
pubmed: 33112236
Science. 2021 Feb 19;371(6531):850-854
pubmed: 33495308
Science. 2021 Aug 13;373(6556):818-823
pubmed: 34016740
Nat Commun. 2021 Jun 21;12(1):3815
pubmed: 34155209
Viruses. 2021 Mar 26;13(4):
pubmed: 33810465
J Travel Med. 2021 Oct 11;28(7):
pubmed: 34230972
iScience. 2021 May 21;24(5):102479
pubmed: 33937725
Nature. 2021 Apr;592(7854):438-443
pubmed: 33690265
N Engl J Med. 2021 Jan 21;384(3):229-237
pubmed: 33113295
Proteins. 2017 Jan;85(1):30-38
pubmed: 27717001
Cureus. 2021 May 10;13(5):e14933
pubmed: 33981518
Mol Cell. 2020 Dec 17;80(6):1136-1138
pubmed: 33338403
Cell Host Microbe. 2021 May 12;29(5):819-833.e7
pubmed: 33789084
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):
pubmed: 34417349
Toxins (Basel). 2016 Mar 03;8(3):
pubmed: 26950154
Cell Host Microbe. 2021 Mar 10;29(3):477-488.e4
pubmed: 33535027
Science. 2021 May 21;372(6544):815-821
pubmed: 33853970
Science. 2020 Nov 27;370(6520):1110-1115
pubmed: 33037066
Cell Mol Immunol. 2020 Jun;17(6):647-649
pubmed: 32313207
Cell Host Microbe. 2021 May 12;29(5):747-751.e4
pubmed: 33887205
Nat Commun. 2021 Feb 11;12(1):944
pubmed: 33574228
N Engl J Med. 2021 Jan 21;384(3):238-251
pubmed: 33332778
Cell Rep. 2020 Oct 20;33(3):108274
pubmed: 33027617
Cell Rep Med. 2021 Apr 20;2(4):100255
pubmed: 33842902
Nat Commun. 2020 Aug 27;11(1):4303
pubmed: 32855401
Nat Med. 2021 Apr;27(4):717-726
pubmed: 33664494
Cell Rep. 2021 Mar 23;34(12):108890
pubmed: 33713594
Virol Sin. 2020 Dec;35(6):768-775
pubmed: 32865701
Glob Chall. 2017 Jan 10;1(1):33-46
pubmed: 31565258
Sci Transl Med. 2021 May 12;13(593):
pubmed: 33820835
Nat Microbiol. 2020 Nov;5(11):1403-1407
pubmed: 32669681
Cell. 2021 Apr 29;184(9):2332-2347.e16
pubmed: 33761326
Bioinformatics. 2019 May 1;35(9):1591-1593
pubmed: 30951584