Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting.

Animals COVID-19 Mice Mice, Inbred BALB C SARS-CoV-2 Spike Glycoprotein, Coronavirus Viral Envelope Proteins
CP: Immunology SARS-CoV-2 coronavirus glycan immune focusing immunogen design

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
22 03 2022
Historique:
received: 02 11 2021
revised: 18 01 2022
accepted: 02 03 2022
pubmed: 19 3 2022
medline: 31 3 2022
entrez: 18 3 2022
Statut: ppublish

Résumé

Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes.

Identifiants

DOI: 10.1016/j.celrep.2022.110561 PMID: 35303475 PMC: PMC8898741
pubmed: 35303475
pii: S2211-1247(22)00305-9
doi: 10.1016/j.celrep.2022.110561
pmc: PMC8898741
pii:
doi:

Substances chimiques

Spike Glycoprotein, Coronavirus 0
Viral Envelope Proteins 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

110561

Subventions

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 : F31 AI138368
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI157155
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 : NIH HHS
ID : S10 OD021527
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 : NIDA NIH HHS
ID : DP2 DA042422
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008313
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124378
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States

Commentaires et corrections

Type : UpdateOf

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., T.M.C., and A.G.S. have filed a provisional patent for the described immunogens. M.S.D. is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Moderna, and Emergent BioSolutions.

Références

N Engl J Med. 2021 Nov 4;385(19):1761-1773
pubmed: 34525277
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Emerg Infect Dis. 2007 Oct;13(10):1562-4
pubmed: 18258008
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
pubmed: 15299374
Science. 2021 Aug 27;373(6558):991-998
pubmed: 34214046
J Virol. 2004 Oct;78(19):10628-35
pubmed: 15367630
J Exp Med. 2021 Dec 6;218(12):
pubmed: 34623376
Science. 2021 Aug 13;373(6556):818-823
pubmed: 34016740
Cell Rep. 2015 Dec 29;13(12):2842-50
pubmed: 26711348
Cell. 2021 Apr 29;184(9):2372-2383.e9
pubmed: 33743213
Am Rev Respir Dis. 1972 May;105(5):805-11
pubmed: 5020629
MMWR Morb Mortal Wkly Rep. 2021 Aug 27;70(34):1163-1166
pubmed: 34437519
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):72-82
pubmed: 16369096
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92
pubmed: 21460446
Cell. 2020 Nov 25;183(5):1367-1382.e17
pubmed: 33160446
N Engl J Med. 2021 Aug 12;385(7):664-666
pubmed: 34233096
Front Immunol. 2014 Apr 22;5:170
pubmed: 24795717
N Engl J Med. 2021 Jul 8;385(2):187-189
pubmed: 33951357
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
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nat Med. 2021 Apr;27(4):622-625
pubmed: 33654292
J Infect Dis. 1974 Mar;129(3):271-6
pubmed: 4816305
Cell. 2021 Apr 29;184(9):2316-2331.e15
pubmed: 33773105
Immunity. 2020 Aug 18;53(2):248-263
pubmed: 32717182
Science. 2021 Feb 12;371(6530):735-741
pubmed: 33436524
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Am J Epidemiol. 1986 May;123(5):862-8
pubmed: 3008551
PLoS Pathog. 2020 Dec 4;16(12):e1009089
pubmed: 33275640
Cell. 2021 Jan 21;184(2):476-488.e11
pubmed: 33412089
Science. 2020 Aug 7;369(6504):650-655
pubmed: 32571838
N Engl J Med. 2014 Aug 28;371(9):828-35
pubmed: 25162889
Nat Protoc. 2016 Feb;11(2):193-213
pubmed: 26741406
Cell. 2015 May 21;161(5):1026-1034
pubmed: 25959776
Cell. 2020 Aug 6;182(3):744-753.e4
pubmed: 32553273
Bioconjug Chem. 2021 May 19;32(5):1034-1046
pubmed: 33951913
Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):61-9
pubmed: 18094468
Nature. 2014 Mar 13;507(7491):201-6
pubmed: 24499818
Science. 2021 Feb 19;371(6531):823-829
pubmed: 33495307
Nature. 2020 Oct;586(7830):572-577
pubmed: 32726802
Science. 2020 Aug 7;369(6504):731-736
pubmed: 32540900
Cell. 2020 Oct 1;183(1):143-157.e13
pubmed: 32877699
Nat Med. 2021 Dec;27(12):2127-2135
pubmed: 34650248
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
J Immunol Methods. 2009 Oct 31;350(1-2):183-93
pubmed: 19716372
Cell. 2020 Aug 6;182(3):722-733.e11
pubmed: 32645327
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
Epidemiol Infect. 1990 Oct;105(2):435-46
pubmed: 2170159
Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):E690-7
pubmed: 22366317
MMWR Morb Mortal Wkly Rep. 2021 Aug 27;70(34):1150-1155
pubmed: 34437517
Nature. 2013 Mar 14;495(7440):251-4
pubmed: 23486063
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):133-44
pubmed: 20124693
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Nat Med. 2021 May;27(5):917-924
pubmed: 33772244
Sci Transl Med. 2022 Aug 10;14(657):eabl9605
pubmed: 35947674
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7
pubmed: 20876137
Sci Transl Med. 2022 Jan 26;14(629):eabj7125
pubmed: 34726473
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
ACS Infect Dis. 2020 May 8;6(5):1182-1191
pubmed: 32267676
Immunity. 2020 Dec 15;53(6):1272-1280.e5
pubmed: 33242394
Nature. 2021 Jun;594(7864):553-559
pubmed: 33971664
Nature. 2021 Apr;592(7855):616-622
pubmed: 33567448
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. 2021 Apr 29;184(9):2348-2361.e6
pubmed: 33730597
J Exp Med. 1956 Aug 1;104(2):199-209
pubmed: 13345965
Cell. 2021 Apr 15;184(8):2201-2211.e7
pubmed: 33743891
J Immunol Methods. 2008 Dec 31;339(2):205-19
pubmed: 18926828
Cell Host Microbe. 2019 Jun 12;25(6):827-835.e6
pubmed: 31104946
Cell Mol Immunol. 2021 Mar;18(3):749-751
pubmed: 33580169
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Immunity. 2020 Dec 15;53(6):1315-1330.e9
pubmed: 33275896
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Sci Transl Med. 2021 Jun 30;13(600):
pubmed: 34103407
ACS Nano. 2021 Feb 23;15(2):2738-2752
pubmed: 33464829
Adv Mater. 2020 Dec;32(50):e2005637
pubmed: 33111375
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
MMWR Morb Mortal Wkly Rep. 2021 Aug 06;70(31):1059-1062
pubmed: 34351882
Nat Med. 2021 Apr;27(4):717-726
pubmed: 33664494
Nat Med. 2015 Dec;21(12):1508-13
pubmed: 26552008
N Engl J Med. 2021 Mar 17;384(15):1468-1470
pubmed: 33730471
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
J Immunol. 1966 Aug;97(2):177-83
pubmed: 5921310
J Biomol Screen. 2013 Apr;18(4):453-61
pubmed: 23112084
Immunity. 2019 Oct 15;51(4):735-749.e8
pubmed: 31563464
Sci Transl Med. 2021 May 12;13(593):
pubmed: 33820835
Cell. 2021 Oct 14;184(21):5432-5447.e16
pubmed: 34619077
J Exp Med. 1966 Sep 1;124(3):331-45
pubmed: 5922742
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
MMWR Morb Mortal Wkly Rep. 2021 Oct 01;70(39):1379-1384
pubmed: 34591835
Nature. 2021 May;593(7857):136-141
pubmed: 33706364
Signal Transduct Target Ther. 2020 Nov 27;5(1):282
pubmed: 33247109
Viruses. 2020 May 06;12(5):
pubmed: 32384820
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
Cell. 2021 Sep 16;184(19):4969-4980.e15
pubmed: 34332650
Immunity. 2020 Apr 14;52(4):583-589
pubmed: 32259480
Nat Immunol. 2020 Nov;21(11):1327-1335
pubmed: 32839612
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701

Auteurs

Blake M Hauser (BM)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Maya Sangesland (M)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Kerri J St Denis (KJ)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Evan C Lam (EC)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

James Brett Case (JB)

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Ian W Windsor (IW)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.

Jared Feldman (J)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Timothy M Caradonna (TM)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Ty Kannegieter (T)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Michael S Diamond (MS)

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Alejandro B Balazs (AB)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Daniel Lingwood (D)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Aaron G Schmidt (AG)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: aschmidt@crystal.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Rationally designed immunogens enable immune...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Rationally designed immunogens enable immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Rationally designed immunogens enable immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Rationally designed immunogens enable immune...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Rationally designed immunogens enable immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Glycoprotéine de spicule des coronavirus › Rationally designed immunogens enable immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Rationally designed immunogens enable immune...