N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.
COVID-19
N-terminal domain
NTD
SARS-CoV-2
memory B cells
neutralizing antibody
spike glycoprotein
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
29 04 2021
29 04 2021
Historique:
received:
07
01
2021
revised:
17
02
2021
accepted:
09
03
2021
pubmed:
25
3
2021
medline:
14
5
2021
entrez:
24
3
2021
Statut:
ppublish
Résumé
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
Identifiants
pubmed: 33761326
pii: S0092-8674(21)00356-1
doi: 10.1016/j.cell.2021.03.028
pmc: PMC7962585
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antigens, Viral
0
RNA, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2332-2347.e16Subventions
Organisme : NIH HHS
ID : S10 OD023476
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008268
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.D.M., F.A.L., D.P., M.B., F.Z., J.d.I., M.M.-R., J.Z., L.E.R., S.B., B.G., C.S.F., F.B., E.C., G.S., A.T., H.W.V., D.C., and M.S.P. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. D.C. is currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this manuscript. The Neyts laboratories have received sponsored research agreements from Vir Biotechnology Inc. H.W.V. is a founder of PierianDx and Casma Therapeutics. Neither company provided funding for this work or is performing related work. D.V. is a consultant for Vir Biotechnology Inc. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Nat Commun. 2020 Oct 21;11(1):5337
pubmed: 33087721
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Elife. 2020 Oct 28;9:
pubmed: 33112236
Nat Methods. 2012 Sep;9(9):853-4
pubmed: 22842542
Science. 2021 Feb 19;371(6531):850-854
pubmed: 33495308
Nature. 2021 Apr;592(7852):116-121
pubmed: 33106671
J Virol. 2018 Apr 27;92(10):
pubmed: 29514901
Science. 2020 Nov 13;370(6518):856-860
pubmed: 33082293
N Engl J Med. 2020 Oct 15;383(16):1544-1555
pubmed: 32722908
Structure. 2019 Jan 2;27(1):134-139.e3
pubmed: 30344107
Cell. 2020 Nov 25;183(5):1367-1382.e17
pubmed: 33160446
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Mol Cell. 2020 May 21;78(4):779-784.e5
pubmed: 32362314
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
Nat Med. 2021 Apr;27(4):622-625
pubmed: 33654292
Nature. 2020 Oct;586(7830):567-571
pubmed: 32756549
Nat Commun. 2020 May 4;11(1):2251
pubmed: 32366817
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Science. 2020 Nov 13;370(6518):861-865
pubmed: 33082294
Cell. 2021 Apr 1;184(7):1804-1820.e16
pubmed: 33691139
Elife. 2016 Sep 26;5:
pubmed: 27669148
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Science. 2020 Aug 7;369(6504):650-655
pubmed: 32571838
Cell Rep. 2019 Sep 24;28(13):3395-3405.e6
pubmed: 31553909
Nature. 2020 Aug;584(7821):450-456
pubmed: 32698192
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Microbiol Spectr. 2016 Dec;4(6):
pubmed: 28087938
Sci Transl Med. 2020 Aug 5;12(555):
pubmed: 32690628
Cell. 2020 Aug 20;182(4):812-827.e19
pubmed: 32697968
Cell Host Microbe. 2021 Mar 10;29(3):463-476.e6
pubmed: 33592168
Science. 2020 Aug 7;369(6504):731-736
pubmed: 32540900
Cell. 2020 Nov 12;183(4):1043-1057.e15
pubmed: 32970989
Nat Methods. 2015 Oct;12(10):943-6
pubmed: 26280328
Bio Protoc. 2016 Dec 5;6(23):
pubmed: 28018942
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):
pubmed: 34417349
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
IUCrJ. 2019 Jan 01;6(Pt 1):5-17
pubmed: 30713699
Nat Methods. 2015 Apr;12(4):361-365
pubmed: 25707030
Nat Commun. 2019 Jul 11;10(1):3068
pubmed: 31296843
Emerg Microbes Infect. 2017 May 24;6(5):e37
pubmed: 28536429
Cell. 2020 Dec 23;183(7):1901-1912.e9
pubmed: 33248470
Science. 2020 Aug 21;369(6506):1014-1018
pubmed: 32540904
Cell Host Microbe. 2020 Sep 9;28(3):445-454.e6
pubmed: 32585135
Cell Host Microbe. 2021 Mar 10;29(3):477-488.e4
pubmed: 33535027
Nat Struct Mol Biol. 2020 Oct;27(10):942-949
pubmed: 32753755
Vaccine. 2017 Jan 3;35(1):10-18
pubmed: 27899228
PLoS Med. 2006 Jul;3(7):e237
pubmed: 16796401
Science. 2020 Aug 21;369(6506):956-963
pubmed: 32540903
Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5
pubmed: 32735849
Science. 2020 Nov 27;370(6520):1110-1115
pubmed: 33037066
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
Nat Biotechnol. 2019 Apr;37(4):420-423
pubmed: 30778233
Nat Struct Mol Biol. 2020 Aug;27(8):763-767
pubmed: 32647346
Natl Sci Rev. 2021 Mar 27;8(8):nwab053
pubmed: 34676098
Science. 2020 Jun 12;368(6496):1274-1278
pubmed: 32404477
Nature. 2020 Dec;588(7838):485-490
pubmed: 33032297
Adv Virus Res. 2019;105:93-116
pubmed: 31522710
Science. 2020 Nov 20;370(6519):950-957
pubmed: 32972994
Nat Commun. 2020 Oct 15;11(1):5214
pubmed: 33060595
Cell. 2020 Sep 3;182(5):1295-1310.e20
pubmed: 32841599
Science. 2021 Jun 4;372(6546):1108-1112
pubmed: 33947773
Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9
pubmed: 33259788
N Engl J Med. 2020 Dec 10;383(24):2320-2332
pubmed: 32877576
Nature. 2020 Aug;584(7821):443-449
pubmed: 32668443
Nature. 2020 Oct;586(7830):583-588
pubmed: 32731257
J Exp Med. 2021 Mar 1;218(3):
pubmed: 33211088
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Cell. 2020 Oct 1;183(1):169-184.e13
pubmed: 32931734
Elife. 2018 Nov 09;7:
pubmed: 30412051
Nat Commun. 2020 Nov 17;11(1):5838
pubmed: 33203860
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Protein Sci. 2020 Apr;29(4):1069-1078
pubmed: 31730249
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530
pubmed: 29872003
Cell. 2020 Sep 3;182(5):1284-1294.e9
pubmed: 32730807
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Nat Methods. 2020 Dec;17(12):1214-1221
pubmed: 33257830
Science. 2020 Jul 17;369(6501):330-333
pubmed: 32366695
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Nature. 2020 Sep;585(7826):588-590
pubmed: 32698190
Immunity. 2020 Jul 14;53(1):98-105.e5
pubmed: 32561270
Cell. 2020 Oct 29;183(3):739-751.e8
pubmed: 32991842
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Cell. 2020 Aug 20;182(4):828-842.e16
pubmed: 32645326
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
Nat Methods. 2019 Nov;16(11):1146-1152
pubmed: 31591575
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
PLoS Pathog. 2021 May 20;17(5):e1009576
pubmed: 34015061
Nature. 2021 May;593(7857):136-141
pubmed: 33706364
Viruses. 2020 May 06;12(5):
pubmed: 32384820
N Engl J Med. 2020 Dec 3;383(23):2291-2293
pubmed: 33176080
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Cell. 2019 Feb 21;176(5):1026-1039.e15
pubmed: 30712865
Science. 2020 Dec 18;370(6523):1464-1468
pubmed: 33184236
J Struct Biol. 2007 Jan;157(1):281-7
pubmed: 16963278
Science. 2021 Mar 12;371(6534):1139-1142
pubmed: 33536258
Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9430-5
pubmed: 26170284