Broadly Neutralizing Antibodies Targeting New Sites of Vulnerability in Hepatitis C Virus E1E2.
Flaviviridae
broadly neutralizing antibodies
epitope
hepatitis C virus
hepatitis C virus clearance
humoral immunity
neutralizing antibodies
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
21
11
2018
accepted:
01
05
2019
pubmed:
10
5
2019
medline:
27
5
2020
entrez:
10
5
2019
Statut:
epublish
Résumé
Increasing evidence indicates that broadly neutralizing antibodies (bNAbs) play an important role in immune-mediated control of hepatitis C virus (HCV) infection, but the relative contribution of neutralizing antibodies targeting antigenic sites across the HCV envelope (E1 and E2) proteins is unclear. Here, we isolated thirteen E1E2-specific monoclonal antibodies (MAbs) from B cells of a single HCV-infected individual who cleared one genotype 1a infection and then became persistently infected with a second genotype 1a strain. These MAbs bound six distinct discontinuous antigenic sites on the E1 protein, the E2 protein, or the E1E2 heterodimer. Three antigenic sites, designated AS108, AS112 (an N-terminal E1 site), and AS146, were distinct from previously described antigenic regions (ARs) 1 to 5 and E1 sites. Antibodies targeting four sites (AR3, AR4-5, AS108, and AS146) were broadly neutralizing. These MAbs also displayed distinct patterns of relative neutralizing potency (i.e., neutralization profiles) across a panel of diverse HCV strains, which led to complementary neutralizing breadth when they were tested in combination. Overall, this study demonstrates that HCV bNAb epitopes are not restricted to previously described antigenic sites, expanding the number of sites that could be targeted for vaccine development.
Identifiants
pubmed: 31068427
pii: JVI.02070-18
doi: 10.1128/JVI.02070-18
pmc: PMC6600205
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
E1 protein, Hepatitis C virus
0
Epitopes, B-Lymphocyte
0
Hepatitis C Antibodies
0
Hepatitis C Antigens
0
Viral Envelope Proteins
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
Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400058C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127469
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008752
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI088791
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
Références
J Virol. 2000 Nov;74(22):10407-16
pubmed: 11044085
Blood. 2001 Feb 15;97(4):1023-6
pubmed: 11159532
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7271-6
pubmed: 12761383
J Virol. 2004 Jul;78(13):7257-63
pubmed: 15194801
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10149-54
pubmed: 15220475
Clin Infect Dis. 2005 Apr 1;40(7):951-8
pubmed: 15824985
Bioinformatics. 2006 Jun 15;22(12):1540-2
pubmed: 16595560
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6025-30
pubmed: 17392433
Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16269-74
pubmed: 17911260
J Virol. 2008 Jan;82(2):966-73
pubmed: 17977972
Nat Med. 2008 Jan;14(1):25-7
pubmed: 18064037
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):997-1002
pubmed: 18195353
J Virol. 2008 Jun;82(12):6067-72
pubmed: 18385242
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
pubmed: 18503082
Hepatology. 2009 Feb;49(2):364-77
pubmed: 19148942
Gastroenterology. 2009 Jun;136(7):2377-86
pubmed: 19303013
J Virol. 2009 Jun;83(12):6149-60
pubmed: 19321602
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7537-41
pubmed: 19380744
Gastroenterology. 2010 Jan;138(1):315-24
pubmed: 19782080
Nature. 2011 Jun 08;474(7350):S2-4
pubmed: 21666731
J Virol. 2011 Oct;85(20):10451-63
pubmed: 21813602
J Infect Dis. 2012 Mar 1;205(5):763-71
pubmed: 22293431
Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6205-10
pubmed: 22492964
PLoS Pathog. 2012;8(4):e1002653
pubmed: 22511875
Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9499-504
pubmed: 22623528
Mol Immunol. 2013 Jan;53(1-2):24-34
pubmed: 22784991
J Virol. 2013 Jan;87(1):37-51
pubmed: 23097455
PLoS Pathog. 2013;9(5):e1003364
pubmed: 23696737
AIDS. 2013 Oct 23;27(16):2551-7
pubmed: 23736152
Hepatology. 2014 Jun;59(6):2140-51
pubmed: 24425349
Immunology. 2014 Sep;143(1):13-20
pubmed: 24854488
J Clin Invest. 2015 Jan;125(1):437-47
pubmed: 25500884
Curr Opin Virol. 2015 Apr;11:148-57
pubmed: 25932568
J Mol Biol. 2015 Aug 14;427(16):2617-28
pubmed: 26135247
J Infect. 2015 Nov;71(5):571-7
pubmed: 26212868
Hepatology. 2015 Dec;62(6):1670-82
pubmed: 26251214
J Virol. 2016 Jan 06;90(6):3112-22
pubmed: 26739044
J Hepatol. 2016 May;64(5):1020-1026
pubmed: 26780289
J Virol. 2016 Jan 27;90(7):3773-82
pubmed: 26819308
Hepatology. 2016 Dec;64(6):1881-1892
pubmed: 27351277
Nat Protoc. 2016 Sep;11(9):1599-616
pubmed: 27490633
PLoS One. 2016 Oct 24;11(10):e0165047
pubmed: 27776169
Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E6946-E6954
pubmed: 27791171
J Viral Hepat. 2017 May;24(5):359-370
pubmed: 28027424
PLoS Pathog. 2017 Feb 24;13(2):e1006235
pubmed: 28235087
JCI Insight. 2017 May 4;2(9):null
pubmed: 28469084
J Virus Erad. 2017 Jul 1;3(3):117-123
pubmed: 28758018
Infect Genet Evol. 2018 Mar;58:77-82
pubmed: 29253674
PLoS Pathog. 2017 Dec 18;13(12):e1006735
pubmed: 29253863
Trends Microbiol. 2018 Oct;26(10):854-864
pubmed: 29703495
Cell Host Microbe. 2018 Nov 14;24(5):703-716.e3
pubmed: 30439340
Cell Host Microbe. 2018 Nov 14;24(5):717-730.e5
pubmed: 30439341