Cross-reactive SARS-CoV-2 epitope targeted across donors informs immunogen design.
SARS-CoV-2
antibody
coronavirus
cross-reactive
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
20 12 2022
20 12 2022
Historique:
received:
14
04
2022
revised:
07
09
2022
accepted:
08
11
2022
pubmed:
25
11
2022
medline:
24
12
2022
entrez:
24
11
2022
Statut:
ppublish
Résumé
The emergence of the antigenically distinct and highly transmissible Omicron variant highlights the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape due to viral evolution. This continued evolution, along with the possible introduction of new sarbecoviruses from zoonotic reservoirs, may evade host immunity elicited by current SARS-CoV-2 vaccines. Identifying cross-reactive antibodies and defining their epitope(s) can provide templates for rational immunogen design strategies for next-generation vaccines. Here, we characterize the receptor-binding-domain-directed, cross-reactive humoral repertoire across 10 human vaccinated donors. We identify cross-reactive antibodies from diverse gene rearrangements targeting two conserved receptor-binding domain epitopes. An engineered immunogen enriches antibody responses to one of these conserved epitopes in mice with pre-existing SARS-CoV-2 immunity; elicited responses neutralize SARS-CoV-2, variants, and related sarbecoviruses. These data show how immune focusing to a conserved epitope targeted by human cross-reactive antibodies may guide pan-sarbecovirus vaccine development, providing a template for identifying such epitopes and translating to immunogen design.
Identifiants
pubmed: 36423634
pii: S2666-3791(22)00398-6
doi: 10.1016/j.xcrm.2022.100834
pmc: PMC9663748
pii:
doi:
Substances chimiques
Epitopes
0
COVID-19 Vaccines
0
Antibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100834Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153098
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155447
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007245
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI160908
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146779
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA040254
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM144273
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124378
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI060354
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests B.M.H. and A.G.S. have filed a provisional patent for the described immunogens.
Références
Cell. 2021 Apr 29;184(9):2372-2383.e9
pubmed: 33743213
Cell. 2021 Jan 21;184(2):476-488.e11
pubmed: 33412089
Nat Commun. 2021 Jun 18;12(1):3781
pubmed: 34145263
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Sci Immunol. 2022 Aug 12;7(74):eabo3425
pubmed: 35536154
Cell. 2021 Sep 16;184(19):4969-4980.e15
pubmed: 34332650
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Nature. 2020 Aug;584(7821):437-442
pubmed: 32555388
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
J Virol. 2004 Oct;78(19):10628-35
pubmed: 15367630
Cell Rep. 2015 Dec 29;13(12):2842-50
pubmed: 26711348
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Annu Rev Biophys. 2018 May 20;47:499-523
pubmed: 29595997
J Biol Chem. 2015 Mar 20;290(12):7436-42
pubmed: 25635058
Nature. 2022 Feb;602(7898):664-670
pubmed: 35016195
Cell. 2015 May 21;161(5):1026-1034
pubmed: 25959776
Nature. 2021 Dec;600(7889):517-522
pubmed: 34619745
Cell. 2022 Mar 17;185(6):1025-1040.e14
pubmed: 35148837
Cell. 2022 Feb 3;185(3):467-484.e15
pubmed: 35081335
Nature. 2022 Feb;602(7898):671-675
pubmed: 35016199
Nature. 2022 Feb;602(7898):654-656
pubmed: 35016196
Nature. 2022 Feb;602(7898):682-688
pubmed: 35016197
Nature. 2014 Mar 13;507(7491):201-6
pubmed: 24499818
Science. 2021 Feb 19;371(6531):823-829
pubmed: 33495307
Nature. 2013 Nov 28;503(7477):535-8
pubmed: 24172901
Science. 2020 Aug 7;369(6504):731-736
pubmed: 32540900
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
Science. 2023 Oct 6;382(6666):eadj0070
pubmed: 37797027
N Engl J Med. 2022 Feb 17;386(7):698-700
pubmed: 35021005
Immunity. 2020 Dec 15;53(6):1272-1280.e5
pubmed: 33242394
Science. 2022 Jan 21;375(6578):eabl6251
pubmed: 34855508
Nature. 2021 Apr;592(7855):616-622
pubmed: 33567448
J Immunol Methods. 2008 Jan 1;329(1-2):112-24
pubmed: 17996249
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3048-53
pubmed: 26976607
Science. 2020 Jun 12;368(6496):1274-1278
pubmed: 32404477
Cell Rep. 2022 Mar 22;38(12):110561
pubmed: 35303475
Nature. 2021 Dec;600(7889):512-516
pubmed: 34544114
Nature. 2022 Feb;602(7898):657-663
pubmed: 35016194
Nat Protoc. 2009;4(3):372-84
pubmed: 19247287
Nature. 2022 Mar;603(7903):913-918
pubmed: 35114688
J Exp Med. 1956 Aug 1;104(2):199-209
pubmed: 13345965
Cell Host Microbe. 2019 Jun 12;25(6):827-835.e6
pubmed: 31104946
Sci Transl Med. 2021 Jun 30;13(600):
pubmed: 34103407
N Engl J Med. 2021 Oct 7;385(15):1401-1406
pubmed: 34407341
Science. 2022 Mar 4;375(6584):1048-1053
pubmed: 35133176
Nat Med. 2022 Mar;28(3):490-495
pubmed: 35046573
Cell. 2022 Feb 3;185(3):457-466.e4
pubmed: 34995482
Nat Med. 2015 Dec;21(12):1508-13
pubmed: 26552008
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
J Immunol. 1966 Aug;97(2):177-83
pubmed: 5921310
Cell Host Microbe. 2022 Jun 8;30(6):880-886.e4
pubmed: 35436444
J Biomol Screen. 2013 Apr;18(4):453-61
pubmed: 23112084
Sci Transl Med. 2021 May 12;13(593):
pubmed: 33820835
J Exp Med. 1966 Sep 1;124(3):331-45
pubmed: 5922742