Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein.

Sheng Jiang, Shuting Wu, Gan Zhao, Yue He, Xinrong Guo, Zhiyu Zhang, Jiawang Hou, Yuan Ding, Alex Cheng, Bin Wang
Author Information
  1. Sheng Jiang: Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College (SHMC), Fudan University, Shanghai, People's Republic of China.
  2. Shuting Wu: Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College (SHMC), Fudan University, Shanghai, People's Republic of China.
  3. Gan Zhao: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  4. Yue He: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  5. Xinrong Guo: Colby College, Waterville, ME, USA.
  6. Zhiyu Zhang: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  7. Jiawang Hou: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  8. Yuan Ding: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  9. Alex Cheng: Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, Jiangsu Province, People's Republic of China.
  10. Bin Wang: Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College (SHMC), Fudan University, Shanghai, People's Republic of China. ORCID

Abstract

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

Keywords

References

  1. Cell Res. 2020 Oct;30(10):936-939 [PMID: 32801356]
  2. J Exp Med. 1993 Dec 1;178(6):1877-92 [PMID: 8245770]
  3. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6880-5 [PMID: 9192660]
  4. Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):542-544 [PMID: 33086866]
  5. Ann Intern Med. 2020 Sep 1;173(5):362-367 [PMID: 32491919]
  6. Cell. 2020 Nov 12;183(4):1058-1069.e19 [PMID: 33058755]
  7. Nucleic Acids Res. 2020 Jul 2;48(W1):W449-W454 [PMID: 32406916]
  8. Eur J Immunol. 2006 Mar;36(3):544-57 [PMID: 16479539]
  9. Biochem Biophys Res Commun. 2021 Jan 29;538:211-217 [PMID: 33190827]
  10. Methods. 2013 Jun 1;61(2):105-9 [PMID: 23454288]
  11. Nat Commun. 2020 May 20;11(1):2601 [PMID: 32433465]
  12. Adv Mater. 2020 Dec;32(50):e2005637 [PMID: 33111375]
  13. J Virol. 2011 Jun;85(11):5446-55 [PMID: 21450826]
  14. Blood. 2016 Jun 30;127(26):3331-40 [PMID: 27207801]
  15. Front Immunol. 2019 Jul 17;10:1678 [PMID: 31379867]
  16. J Vis Exp. 2018 Oct 17;(140): [PMID: 30394402]
  17. Immunity. 1998 May;8(5):553-62 [PMID: 9620676]
  18. J Infect Dis. 2020 May 11;221(11):1762-1769 [PMID: 32227123]
  19. N Engl J Med. 2020 Mar 26;382(13):1199-1207 [PMID: 31995857]
  20. Sci Immunol. 2021 Mar 4;6(57): [PMID: 33664060]
  21. Nat Commun. 2020 Aug 14;11(1):4081 [PMID: 32796842]
  22. Nat Commun. 2017 Nov 13;8(1):1459 [PMID: 29129917]
  23. J Microbiol. 2008 Dec;46(6):728-36 [PMID: 19107404]
  24. Respir Res. 2020 Mar 26;21(1):74 [PMID: 32216803]
  25. Nature. 2021 Aug;596(7871):268-272 [PMID: 34107529]
  26. Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3112-3117 [PMID: 30718433]
  27. Immunity. 2021 Feb 9;54(2):340-354.e6 [PMID: 33567252]
  28. Vaccine. 2020 Nov 17;38(49):7697-7701 [PMID: 33164796]
  29. Cureus. 2020 Mar 26;12(3):e7423 [PMID: 32337143]

MeSH Term

COVID-19
COVID-19 Vaccines
Epitopes, T-Lymphocyte
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Chemicals

COVID-19 Vaccines
Epitopes, T-Lymphocyte
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Word Cloud

Created with Highcharts 10.0.0epitopesepitopeSARS-CoV-2CTLCOVID-19spikeproteinTMHC-IconserveddiseasevariantswithincellseveralpotentialHLAallelescellularcausedinfectiondevastatingglobalpublichealtheconomydatehundredvaccinesknowndevelopmentapprovedfightusingprimarytargetantigenAlthoughvirus-neutralizingmainlylocatedRBDpresenceparticularlylikelyneededkillinginfectedcellsreceivedcomparativelylittleattentionstudypredictedweb-basedanalytictoolsnarrowedMHC-IIELIspotcytolyticassayshighlycurrentviralcompatiblepresentationworldwideconclusionidentifiedsuitableevaluatingCD8+cell-mediatedresponsepotentiallyadditionfuturevaccinecandidatesmaximizeresponsesIdentificationpromiscuousSpikeimmunity

Similar Articles

Cited By