Vaccine elicitation and structural basis for antibody protection against alphaviruses.
alphavirus
broadly neutralizing antibody
cryo-EM
in vivo challenge
vaccine
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 06 2023
08 06 2023
Historique:
received:
28
09
2022
revised:
03
03
2023
accepted:
12
05
2023
pmc-release:
08
06
2024
medline:
12
6
2023
pubmed:
10
6
2023
entrez:
9
6
2023
Statut:
ppublish
Résumé
Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses.
Identifiants
pubmed: 37295404
pii: S0092-8674(23)00538-X
doi: 10.1016/j.cell.2023.05.019
pmc: PMC10411218
mid: NIHMS1906962
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2672-2689.e25Subventions
Organisme : Intramural NIH HHS
ID : ZIA AI005022
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests NIH has submitted a provisional patent application for select antibodies described in this manuscript on which M.S.S., S.K., R.V., P.D.K., and M.R. are co-inventors.
Références
Nature. 2010 Dec 2;468(7324):709-12
pubmed: 21124458
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530
pubmed: 29872003
Nat Med. 2010 Mar;16(3):334-8
pubmed: 20111039
Viruses. 2019 Mar 28;11(4):
pubmed: 30925717
Vector Borne Zoonotic Dis. 2006 Winter;6(4):325-37
pubmed: 17187566
PLoS Pathog. 2020 Aug 6;16(8):e1008743
pubmed: 32760128
J Neuroimmunol. 2017 Jul 15;308:118-130
pubmed: 28501330
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68
pubmed: 15572779
Vaccine. 2011 Jan 17;29(4):813-20
pubmed: 21084062
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
mBio. 2013 Jul 02;4(4):
pubmed: 23820395
Viruses. 2019 Nov 13;11(11):
pubmed: 31766138
Rev Sci Tech. 2015 Aug;34(2):491-501
pubmed: 26601451
Nature. 2018 May;557(7706):570-574
pubmed: 29769725
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W615-9
pubmed: 15215462
Nat Methods. 2014 Jan;11(1):63-5
pubmed: 24213166
Antiviral Res. 2012 Jun;94(3):242-57
pubmed: 22522323
J Virol. 2014 Oct;88(20):12077-86
pubmed: 25122801
Antiviral Res. 2008 Jun;78(3):230-41
pubmed: 18313150
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Immunol. 2016 Dec 1;197(11):4210-4218
pubmed: 27864552
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
J Virol. 1975 Jul;16(1):141-5
pubmed: 48559
Lancet Infect Dis. 2021 May;21(5):e123-e133
pubmed: 33160445
Science. 2012 Sep 14;337(6100):1343-8
pubmed: 22878502
Cell Rep. 2021 Apr 6;35(1):108962
pubmed: 33826892
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Nat Methods. 2022 Jun;19(6):679-682
pubmed: 35637307
Elife. 2019 Oct 09;8:
pubmed: 31596239
Lancet. 2014 Dec 6;384(9959):2046-52
pubmed: 25132507
Vaccine. 2014 Jan 9;32(3):311-9
pubmed: 24295803
Front Microbiol. 2016 Jun 20;7:959
pubmed: 27379085
Viruses. 2018 Mar 24;10(4):
pubmed: 29587363
Nucleic Acids Res. 2016 Jul 8;44(W1):W474-8
pubmed: 27131379
Antiviral Res. 2003 Jan;57(1-2):101-11
pubmed: 12615306
Cell. 2015 Nov 19;163(5):1095-1107
pubmed: 26553503
Cell Host Microbe. 2020 Mar 11;27(3):428-440.e9
pubmed: 32075743
Immunity. 2019 Oct 15;51(4):724-734.e4
pubmed: 31586542
Nature. 2004 Jan 22;427(6972):320-5
pubmed: 14737160
Nat Rev Microbiol. 2004 Oct;2(10):789-801
pubmed: 15378043
PLoS Pathog. 2007 Dec;3(12):e201
pubmed: 18069894
Annu Rev Entomol. 2004;49:141-74
pubmed: 14651460
Cell. 2021 Aug 19;184(17):4414-4429.e19
pubmed: 34416146
Viruses. 2022 Jul 08;14(7):
pubmed: 35891482
Nature. 1986 Apr 10-16;320(6062):533-5
pubmed: 3960136
Cell Rep. 2019 Sep 3;28(10):2647-2658.e5
pubmed: 31484075
Vaccine. 2009 Aug 6;27(36):4879-82
pubmed: 19576665
Cell. 2021 Aug 19;184(17):4430-4446.e22
pubmed: 34416147
Viruses. 2020 Sep 13;12(9):
pubmed: 32933112
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
NPJ Vaccines. 2022 Apr 22;7(1):46
pubmed: 35459271
Commun Biol. 2021 Jul 15;4(1):874
pubmed: 34267316
Nature. 1998 Jun 18;393(6686):648-59
pubmed: 9641677
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
Sci Immunol. 2019 Feb 22;4(32):
pubmed: 30796092
Cell Host Microbe. 2020 Nov 11;28(5):699-711.e7
pubmed: 32783883
PLoS Pathog. 2019 Dec 2;15(12):e1008157
pubmed: 31790515
Nature. 2020 Dec;588(7837):308-314
pubmed: 33208938
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Vaccine. 2012 Nov 26;30(50):7271-7
pubmed: 23031498
Nature. 2021 Oct;598(7882):677-681
pubmed: 34646021
Ann Clin Microbiol Antimicrob. 2020 May 19;19(1):19
pubmed: 32429942
Virology. 2016 Dec;499:30-39
pubmed: 27632563
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Virulence. 2021 Dec;12(1):430-443
pubmed: 33487119
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):
pubmed: 34507983
Vaccines (Basel). 2020 Jun 03;8(2):
pubmed: 32503232
PLoS Pathog. 2020 Oct 22;16(10):e1008876
pubmed: 33091085
Vet Pathol. 2010 Sep;47(5):790-805
pubmed: 20551475
PLoS Pathog. 2022 Jun 16;18(6):e1010574
pubmed: 35709309
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Vet Pathol. 1998 Sep;35(5):386-97
pubmed: 9754544
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
J Clin Invest. 2017 Mar 1;127(3):737-749
pubmed: 28248203
Immunity. 2020 Oct 13;53(4):733-744.e8
pubmed: 32946741
Nature. 2010 Dec 2;468(7324):705-8
pubmed: 21124457
J Virol. 2006 Jan;80(2):737-49
pubmed: 16378976
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303
pubmed: 29788355
Immunity. 2019 Mar 19;50(3):677-691.e13
pubmed: 30876875
Lancet Infect Dis. 2022 Aug;22(8):1210-1220
pubmed: 35568049
Virology. 1991 Jun;182(2):430-41
pubmed: 1673812
J Struct Biol. 2000 Oct;132(1):33-45
pubmed: 11121305
Sci Transl Med. 2019 May 15;11(492):
pubmed: 31092692
Nat Microbiol. 2019 Jan;4(1):187-197
pubmed: 30455470
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
J Immunol Res. 2018 Jun 3;2018:8521060
pubmed: 29967804
Cell. 2020 Dec 23;183(7):1884-1900.e23
pubmed: 33301709
Viruses. 2010 Mar 26;2(4):796-825
pubmed: 21546978
Comp Med. 2018 Oct 1;68(5):380-395
pubmed: 30282570
Virol J. 2017 Jul 20;14(1):135
pubmed: 28728590
J Virol. 2014 Nov;88(21):12180-92
pubmed: 25142598
Vaccines (Basel). 2020 Sep 02;8(3):
pubmed: 32887313
Cell. 2019 Jun 13;177(7):1725-1737.e16
pubmed: 31080061
N Engl J Med. 2013 May 2;368(18):1670-3
pubmed: 23635048
Science. 2010 Aug 13;329(5993):856-61
pubmed: 20616233
PLoS Pathog. 2013;9(4):e1003312
pubmed: 23637602
Vaccine. 1996 Mar;14(4):337-43
pubmed: 8744562
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701