Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
09 06 2023
09 06 2023
Historique:
medline:
9
6
2023
pubmed:
7
6
2023
entrez:
7
6
2023
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels of S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated in silico and 15 were produced for biochemical analysis. S2D14, which contains 20 computationally designed mutations within the S2 domain and a rationally engineered D614G mutation in the SD2 domain, has an ~11-fold increase in protein yield and retains RBD antigenicity. Cryo-electron microscopy structures reveal a mixture of populations in various RBD conformational states. Vaccination of mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than adjuvanted S-2P against the SARS-CoV-2 Wuhan strain and four variants of concern. S2D14 may be a useful scaffold or tool for the design of future coronavirus vaccines, and the approaches used for the design of S2D14 may be broadly applicable to streamline vaccine discovery.
Identifiants
pubmed: 37285422
doi: 10.1126/sciadv.adg0330
pmc: PMC10246912
doi:
Substances chimiques
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadg0330Références
Viruses. 2022 Jun 18;14(6):
pubmed: 35746806
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Immune Netw. 2021 Oct 11;21(5):e32
pubmed: 34796036
Cell Rep. 2022 Oct 18;41(3):111512
pubmed: 36223774
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Nat Struct Mol Biol. 2021 Feb;28(2):128-131
pubmed: 33402708
Science. 2022 Aug 5;377(6606):eabq0839
pubmed: 35857620
EClinicalMedicine. 2022 Apr;46:101383
pubmed: 35434578
Science. 2022 Jan 28;375(6579):449-454
pubmed: 34990214
Nat Commun. 2022 Mar 14;13(1):1299
pubmed: 35288548
Cell. 2021 Apr 1;184(7):1821-1835.e16
pubmed: 33667349
Cell Rep. 2021 Nov 2;37(5):109928
pubmed: 34706271
Emerg Microbes Infect. 2022 Dec;11(1):477-481
pubmed: 35034583
Mol Ther. 2022 May 4;30(5):1897-1912
pubmed: 34990810
Structure. 2019 Jan 2;27(1):134-139.e3
pubmed: 30344107
Cell. 2020 Nov 25;183(5):1367-1382.e17
pubmed: 33160446
Lancet Microbe. 2021 Jul;2(7):e283-e284
pubmed: 33846703
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Curr Opin Immunol. 2022 Aug;77:102209
pubmed: 35598506
Nature. 2021 Apr;592(7854):438-443
pubmed: 33690265
Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):
pubmed: 34551978
Nat Commun. 2017 Nov 16;8(1):1528
pubmed: 29142300
mSphere. 2020 Sep 16;5(5):
pubmed: 32938700
Vaccine. 2022 Jul 29;40(31):4220-4230
pubmed: 35691871
Sci Immunol. 2020 Jun 11;5(48):
pubmed: 32527802
J Struct Biol. 2015 Nov;192(2):216-21
pubmed: 26278980
Cell Rep. 2022 Aug 23;40(8):111276
pubmed: 35981534
Nat Biotechnol. 2017 Feb;35(2):128-135
pubmed: 28092658
Cell. 1992 Feb 21;68(4):635-45
pubmed: 1739972
PLoS One. 2011;6(6):e20161
pubmed: 21731610
Nat Immunol. 2022 Feb;23(2):186-193
pubmed: 35105982
J Virol. 2002 Sep;76(17):8875-89
pubmed: 12163607
PLoS One. 2011;6(6):e20450
pubmed: 21731614
Nat Commun. 2021 Jan 11;12(1):244
pubmed: 33431842
Nature. 2022 Aug;608(7923):593-602
pubmed: 35714668
Cell. 2020 Dec 10;183(6):1735
pubmed: 33306958
Nat Med. 2021 May;27(5):759-761
pubmed: 33972793
Nat Med. 2021 Dec;27(12):2127-2135
pubmed: 34650248
Cell Host Microbe. 2021 May 12;29(5):819-833.e7
pubmed: 33789084
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
Nature. 2021 Sep;597(7874):97-102
pubmed: 34261126
Sci Adv. 2022 Sep 16;8(37):eabq8276
pubmed: 36103542
Nature. 2021 Sep;597(7874):103-108
pubmed: 34280951
Nat Commun. 2022 Jun 27;13(1):3654
pubmed: 35760812
Nat Methods. 2018 Oct;15(10):816-822
pubmed: 30250057
Nat Commun. 2018 Jul 17;9(1):2780
pubmed: 30018322
J Chem Theory Comput. 2016 Dec 13;12(12):6201-6212
pubmed: 27766851
Signal Transduct Target Ther. 2021 Sep 9;6(1):340
pubmed: 34504054
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Cell Rep. 2021 Jan 26;34(4):108682
pubmed: 33503432
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Sci Adv. 2022 May 6;8(18):eabn2911
pubmed: 35507649
Science. 2020 Nov 20;370(6519):950-957
pubmed: 32972994
Cell. 2020 Sep 3;182(5):1295-1310.e20
pubmed: 32841599
Nature. 2022 Feb;602(7898):657-663
pubmed: 35016194
Nature. 2020 Dec;588(7837):327-330
pubmed: 32942285
Nat Commun. 2021 Aug 10;12(1):4817
pubmed: 34376662
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Proc Natl Acad Sci U S A. 2022 Aug 30;119(35):e2110105119
pubmed: 35994646
Cell Rep. 2021 Nov 2;37(5):109929
pubmed: 34710354
Cell Rep. 2022 Feb 8;38(6):110348
pubmed: 35114110
Emerg Microbes Infect. 2022 Dec;11(1):351-367
pubmed: 34964428
Curr Res Struct Biol. 2020;2:45-55
pubmed: 33688632
Nat Struct Mol Biol. 2020 Oct;27(10):925-933
pubmed: 32699321
Mol Cell. 2016 Jul 21;63(2):337-346
pubmed: 27425410
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Nat Commun. 2022 Sep 17;13(1):5459
pubmed: 36115859
N Engl J Med. 2022 Oct 6;387(14):1279-1291
pubmed: 36112399
J Chem Theory Comput. 2017 Jun 13;13(6):3031-3048
pubmed: 28430426
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
pubmed: 9254694
Expert Rev Vaccines. 2012 Mar;11(3):349-66
pubmed: 22380826
Nat Med. 2023 Feb;29(2):344-347
pubmed: 36473500
PLoS One. 2011;6(12):e28766
pubmed: 22163331
J Med Virol. 2020 Sep;92(9):1386-1390
pubmed: 32311094
Elife. 2022 Aug 25;11:
pubmed: 36004719
Nat Protoc. 2021 Nov;16(11):5339-5356
pubmed: 34611365
Curr Opin Struct Biol. 2021 Aug;69:63-69
pubmed: 33910104
Nat Chem. 2021 Oct;13(10):963-968
pubmed: 34413500
Cell. 2020 Oct 29;183(3):739-751.e8
pubmed: 32991842
Signal Transduct Target Ther. 2022 Jun 6;7(1):172
pubmed: 35665745
Protein Sci. 2014 Jan;23(1):47-55
pubmed: 24265211
Structure. 2013 Oct 8;21(10):1735-42
pubmed: 24035711
mBio. 2020 Sep 25;11(5):
pubmed: 32978311
Cell Rep. 2020 Mar 17;30(11):3755-3765.e7
pubmed: 32187547
J Virol. 2003 Aug;77(16):8801-11
pubmed: 12885899
Nat Biotechnol. 2012 May 27;30(6):543-8
pubmed: 22634563
Nature. 2021 May;593(7858):266-269
pubmed: 33767447
N Engl J Med. 2022 Jun 2;386(22):2097-2111
pubmed: 35507481
J Clin Med. 2022 Jul 18;11(14):
pubmed: 35887928
Science. 2013 Nov 1;342(6158):592-8
pubmed: 24179220
Nature. 2021 Dec;600(7889):530-535
pubmed: 34670266
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701