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Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.
Nat Immunol. 2020 11; 21(11):1336-1345.NI

Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Authors+Show Affiliations

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Beijing You'an Hospital, Capital Medical University, Beijing, China.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. CAMS Key Laboratory of Tumor Immunology and Radiation Therapy, Xinjiang Tumor Hospital, Xinjiang Medical University, Xinjiang, China.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Sequencing and Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Diamond Light Source, Didcot, UK.Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Diamond Light Source, Didcot, UK.York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.The Florey Institute for Host-Pathogen Interactions, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.Sequencing and Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.ProImmune, Oxford, UK.ProImmune, Oxford, UK.NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. Respiratory Medicine, Institute in The Park, Alder Hey Children's Hospital, Liverpool, UK.Anaesthesia, Critical Care and Pain Medicine Division of Health Sciences, University of Edinburgh, Edinburgh, UK.NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Worthing Hospital, Worthing, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Beijing You'an Hospital, Capital Medical University, Beijing, China.Beijing You'an Hospital, Capital Medical University, Beijing, China.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK.No affiliation info availableNo affiliation info availableMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK. Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK.Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Nuffield Department of Medicine, University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Oxford University Hospitals NHS Foundation Trust, Oxford, UK. NIHR Oxford Biomedical Research Centre, Oxford, UK.MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk. Nuffield Department of Medicine, University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32887977

Citation

Peng, Yanchun, et al. "Broad and Strong Memory CD4+ and CD8+ T Cells Induced By SARS-CoV-2 in UK Convalescent Individuals Following COVID-19." Nature Immunology, vol. 21, no. 11, 2020, pp. 1336-1345.
Peng Y, Mentzer AJ, Liu G, et al. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol. 2020;21(11):1336-1345.
Peng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W., Rostron, T., Supasa, P., Liu, C., López-Camacho, C., Slon-Campos, J., Zhao, Y., Stuart, D. I., Paesen, G. C., Grimes, J. M., Antson, A. A., Bayfield, O. W., Hawkins, D. E. D. P., ... Dong, T. (2020). Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nature Immunology, 21(11), 1336-1345. https://doi.org/10.1038/s41590-020-0782-6
Peng Y, et al. Broad and Strong Memory CD4+ and CD8+ T Cells Induced By SARS-CoV-2 in UK Convalescent Individuals Following COVID-19. Nat Immunol. 2020;21(11):1336-1345. PubMed PMID: 32887977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. AU - Peng,Yanchun, AU - Mentzer,Alexander J, AU - Liu,Guihai, AU - Yao,Xuan, AU - Yin,Zixi, AU - Dong,Danning, AU - Dejnirattisai,Wanwisa, AU - Rostron,Timothy, AU - Supasa,Piyada, AU - Liu,Chang, AU - López-Camacho,César, AU - Slon-Campos,Jose, AU - Zhao,Yuguang, AU - Stuart,David I, AU - Paesen,Guido C, AU - Grimes,Jonathan M, AU - Antson,Alfred A, AU - Bayfield,Oliver W, AU - Hawkins,Dorothy E D P, AU - Ker,De-Sheng, AU - Wang,Beibei, AU - Turtle,Lance, AU - Subramaniam,Krishanthi, AU - Thomson,Paul, AU - Zhang,Ping, AU - Dold,Christina, AU - Ratcliff,Jeremy, AU - Simmonds,Peter, AU - de Silva,Thushan, AU - Sopp,Paul, AU - Wellington,Dannielle, AU - Rajapaksa,Ushani, AU - Chen,Yi-Ling, AU - Salio,Mariolina, AU - Napolitani,Giorgio, AU - Paes,Wayne, AU - Borrow,Persephone, AU - Kessler,Benedikt M, AU - Fry,Jeremy W, AU - Schwabe,Nikolai F, AU - Semple,Malcolm G, AU - Baillie,J Kenneth, AU - Moore,Shona C, AU - Openshaw,Peter J M, AU - Ansari,M Azim, AU - Dunachie,Susanna, AU - Barnes,Eleanor, AU - Frater,John, AU - Kerr,Georgina, AU - Goulder,Philip, AU - Lockett,Teresa, AU - Levin,Robert, AU - Zhang,Yonghong, AU - Jing,Ronghua, AU - Ho,Ling-Pei, AU - ,, AU - ,, AU - Cornall,Richard J, AU - Conlon,Christopher P, AU - Klenerman,Paul, AU - Screaton,Gavin R, AU - Mongkolsapaya,Juthathip, AU - McMichael,Andrew, AU - Knight,Julian C, AU - Ogg,Graham, AU - Dong,Tao, Y1 - 2020/09/04/ PY - 2020/06/02/received PY - 2020/08/11/accepted PY - 2020/9/6/pubmed PY - 2020/11/3/medline PY - 2020/9/5/entrez SP - 1336 EP - 1345 JF - Nature immunology JO - Nat Immunol VL - 21 IS - 11 N2 - The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design. SN - 1529-2916 UR - https://www.unboundmedicine.com/medline/citation/32887977/Broad_and_strong_memory_CD4+_and_CD8+_T_cells_induced_by_SARS_CoV_2_in_UK_convalescent_individuals_following_COVID_19_ L2 - https://doi.org/10.1038/s41590-020-0782-6 DB - PRIME DP - Unbound Medicine ER -