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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

DOI: 10.1038/s41590-020-0782-6 DOI Help

Authors: Yanchun Peng (MRC Human Immunology Unit, University of Oxford; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI)) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Guihai Liu (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; Beijing You’an Hospital, Capital Medical University) , Xuan Yao (MRC Human Immunology Unit, University of Oxford; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI)) , Zixi Yin (MRC Human Immunology Unit, University of Oxford; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI)) , Danning Dong (MRC Human Immunology Unit, University of Oxford; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI); Xinjiang Tumor Hospital, Xinjiang Medical University) , Wanwisa Dejnirattisai (University of Oxford) , Timothy Rostron (University of Oxford) , Piyada Supasa (University of Oxford) , Chang Liu (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , César López-camacho (Wellcome Centre for Human Genetics, University of Oxfor) , Jose Slon-campos (University of Oxford) , Yuguang Zhao (University of Oxford) , David I. Stuart (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI); Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source) , Guido C. Paesen (Wellcome Centre for Human Genetics, University of Oxford) , Jonathan M. Grimes (Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source) , Alfred A. Antson (University of York) , Oliver W. Bayfield (University of York) , Dorothy E. D. P. Hawkins (University of York) , De-sheng Ker (University of York) , Beibei Wang (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , Lance Turtle (Liverpool University Hospitals NHS Foundation Trust; University of Liverpool) , Krishanthi Subramaniam (University of Liverpool) , Paul Thomson (University of Liverpool) , Ping Zhang (University of Oxford) , Christina Dold (University of Oxford) , Jeremy Ratcliff (University of Oxford) , Peter Simmonds (University of Oxford) , Thushan De Silva (University of Sheffield) , Paul Sopp (University of Oxford) , Dannielle Wellington (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , Ushani Rajapaksa (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , Yi-ling Chen (University of Oxford) , Mariolina Salio (University of Oxford) , Giorgio Napolitani (University of Oxford) , Wayne Paes (University of Oxford) , Persephone Borrow (University of Oxford) , Benedikt M. Kessler (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , Jeremy W. Fry (ProImmune) , Nikolai F. Schwabe (ProImmune) , Malcolm G. Semple (University of Liverpool; Alder Hey Children’s Hospital) , J. Kenneth Baillie (University of Edinburgh) , Shona C. Moore (University of Liverpool) , Peter J. M. Openshaw (Imperial College London) , M. Azim Ansari (University of Oxford) , Susanna Dunachie (University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Eleanor Barnes (University of Oxford; Oxford University Hospitals NHS Foundation Trust; NIHR Oxford Biomedical Research Centre) , John Frater (University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Georgina Kerr (University of Oxford) , Oliver Gould (University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Teresa Lockett (Oxford University Hospitals NHS Foundation Trust) , Robert Levin (Worthing Hospital) , Yonghong Zhang (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; Beijing You’an Hospital, Capital Medical University) , Ronghua Jing (Beijing You’an Hospital, Capital Medical University) , Ling-pei Ho (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; NIHR Oxford Biomedical Research Centre) , Richard J. Cornall (University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Christopher P. Conlon (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Paul Klenerman (University of Oxford; NIHR Oxford Biomedical Research Centre) , Gavin R. Screaton (University of Oxford; Oxford University Hospitals NHS Foundation Trust; NIHR Oxford Biomedical Research Centre) , Juthathip Mongkolsapaya (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; NIHR Oxford Biomedical Research Centre; Siriraj Hospital, Mahidol University) , Andrew Mcmichael (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford) , Julian C. Knight (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI); Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Graham Ogg (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford; Oxford University Hospitals NHS Foundation Trust; NIHR Oxford Biomedical Research Centre) , Tao Dong (Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Immunology , VOL 7

State: Published (Approved)
Published: September 2020

Open Access Open Access

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.

Journal Keywords: Immunological memory; Viral infection

Subject Areas: Biology and Bio-materials, Medicine


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s41590-020-0782-6.pdf