Lack of antibody-mediated cross-protection between SARS-CoV-2 and SARS-CoV infections.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antibody Specificity
Betacoronavirus
/ genetics
CHO Cells
Cell Line, Tumor
Cricetinae
Cricetulus
Cross Reactions
Female
Humans
Mice
Mice, Inbred BALB C
Severe acute respiratory syndrome-related coronavirus
/ genetics
SARS-CoV-2
Sequence Homology
Spike Glycoprotein, Coronavirus
/ genetics
ACE2
COVID-19
CoV
Cross-neutralization
SARS-CoV-2
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
15
04
2020
revised:
25
05
2020
accepted:
29
06
2020
pubmed:
25
7
2020
medline:
4
9
2020
entrez:
25
7
2020
Statut:
ppublish
Résumé
The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined. Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies. We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice. Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses. This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.
Sections du résumé
BACKGROUND
BACKGROUND
The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined.
METHODS
METHODS
Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies.
FINDINGS
RESULTS
We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice.
INTERPRETATION
CONCLUSIONS
Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses.
FUNDING
BACKGROUND
This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.
Identifiants
pubmed: 32707445
pii: S2352-3964(20)30265-6
doi: 10.1016/j.ebiom.2020.102890
pmc: PMC7372296
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Spike Glycoprotein, Coronavirus
0
spike glycoprotein, SARS-CoV
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102890Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests with respect to this study.
Références
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Lancet. 2020 Feb 22;395(10224):565-574
pubmed: 32007145
Virol J. 2013 Aug 26;10:266
pubmed: 23978242
Nature. 2013 Aug 8;500(7461):227-31
pubmed: 23831647
Vaccine. 2016 Jan 20;34(4):413-423
pubmed: 26691569
Curr Opin Immunol. 2018 Aug;53:74-80
pubmed: 29704764
EMBO J. 2005 Apr 20;24(8):1634-43
pubmed: 15791205
J Pathol. 2004 Jun;203(2):631-7
pubmed: 15141377
Emerg Microbes Infect. 2018 Apr 4;7(1):60
pubmed: 29618723
Nat Rev Microbiol. 2016 Aug;14(8):523-34
pubmed: 27344959
Int J Infect Dis. 2020 Feb;91:264-266
pubmed: 31953166
N Engl J Med. 2020 Mar 5;382(10):970-971
pubmed: 32003551
J Med Virol. 2020 Jun;92(6):595-601
pubmed: 32100877
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
Vaccine. 2006 Jan 30;24(5):652-61
pubmed: 16214268
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
N Engl J Med. 2020 Mar 5;382(10):929-936
pubmed: 32004427
Annu Rev Immunol. 2016 May 20;34:635-59
pubmed: 27168247
Science. 2005 Sep 16;309(5742):1864-8
pubmed: 16166518
J Gen Virol. 2006 Mar;87(Pt 3):641-650
pubmed: 16476986
Cell Host Microbe. 2020 Mar 11;27(3):325-328
pubmed: 32035028
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Sci China Life Sci. 2018 Oct;61(10):1280-1282
pubmed: 30091015
Cell. 2020 May 14;181(4):894-904.e9
pubmed: 32275855
Microbiol Mol Biol Rev. 2016 Oct 26;80(4):989-1010
pubmed: 27784796
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508