RT Journal Article
SR Electronic
T1 Broad and strong memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.05.134551
DO 10.1101/2020.06.05.134551
A1 Yanchun Peng
A1 Alexander J. Mentzer
A1 Guihai Liu
A1 Xuan Yao
A1 Zixi Yin
A1 Danning Dong
A1 Wanwisa Dejnirattisai
A1 Timothy Rostron
A1 Piyada Supasa
A1 Chang Liu
A1 Cesar Lopez-Camacho
A1 Jose Slon-campos
A1 Yuguang Zhao
A1 Dave Stuart
A1 Guido Paeson
A1 Jonathan Grimes
A1 Fred Antson
A1 Oliver W. Bayfield
A1 Dorothy EDP. Hawkins
A1 De-Sheng Ker
A1 Lance Turtle
A1 Krishanthi Subramaniam
A1 Paul Thomson
A1 Ping Zhang
A1 Christina Dold
A1 Jeremy Ratcliff
A1 Peter Simmonds
A1 Thushan de Silva
A1 Paul Sopp
A1 Dannielle Wellington
A1 Ushani Rajapaksa
A1 Yi-Ling Chen
A1 Mariolina Salio
A1 Giorgio Napolitani
A1 Wayne Paes
A1 Persephone Borrow
A1 Benedikt Kessler
A1 Jeremy W. Fry
A1 Nikolai F. Schwabe
A1 Malcolm G Semple
A1 Kenneth J. Baillie
A1 Shona Moore
A1 Peter JM Openshaw
A1 Azim Ansari
A1 Susanna Dunachie
A1 Ellie Barnes
A1 John Frater
A1 Georgina Kerr
A1 Philip Goulder
A1 Teresa Lockett
A1 Robert Levin
A1 Oxford Immunology Network Covid-19 Response T cell Consortium
A1 Richard J. Cornall
A1 Chris Conlon
A1 Paul Klenerman
A1 Andrew McMichael
A1 Gavin Screaton
A1 Juthathip Mongkolsapaya
A1 Julian C. Knight
A1 Graham Ogg
A1 Tao Dong
YR 2020
UL http://biorxiv.org/content/early/2020/06/08/2020.06.05.134551.abstract
AB COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFNγ based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p&lt;0.001, &lt;0.001 and =0.002). We identified 39 separate peptides containing CD4+ and/or CD8+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8+ T cells than spike-specific CD8+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.Competing Interest StatementThe authors have declared no competing interest.