About: Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients

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About: Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients
Creator	Liu, Chang Simmonds, Peter Dong, Tao Klenerman, Paul Borrow, Persephone Liu, Guihai Peng, Yanchun Wellington, Dannielle Dunachie, Susanna Zhang, Ping Frater, John Goulder, Philip Openshaw, Peter Mongkolsapaya, Juthathip Screaton, Gavin Dejnirattisai, Wanwisa Lopez-Camacho, Cesar Zhao, Yuguang Baillie, Kenneth Grimes, Jonathan Kessler, Benedikt Mcmichael, Andrew Semple, Malcolm Moore, Shona Thomson, Paul Turtle, Lance Yin, Zixi De Silva, Thushan Dold, Christina Knight, Julian Mentzer, Alexander Ratcliff, Jeremy Ansari, Azim Antson, Fred Barnes, Ellie Bayfield, Oliver Chen, Yi-Ling Conlon, Chris Cornall, Richard Dong, Danning Fry, Jeremy Napolitani, Giorgio Ogg, Graham Hawkins, Dorothy Ker, De-Sheng Kerr, Georgina Levin, Robert Lockett, Teresa Paes, Wayne Paeson, Guido Rajapaksa, Ushani Rostron, Timothy Salio, Mariolina Schwabe, Nikolai Slon-Campos, Jose Sopp, Paul Stuart, Dave Subramaniam, Krishanthi Supasa, Piyada Yao, Xuan
Source	BioRxiv; Medline; WHO
abstract	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<0.001, <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.
has issue date	2020-06-08(xsd:dateTime)
bibo:doi	10.1101/2020.06.05.134551
bibo:pmid	32577665
has license	biorxiv
sha1sum (hex)	08338d3919d590f618398cc9ea7c7f5064073186
schema:url	https://doi.org/10.1101/2020.06.05.134551
resource representing a document's title	Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients
has PubMed identifier	32577665
schema:publication	bioRxiv
resource representing a document's body	covid:08338d3919d590f618398cc9ea7c7f5064073186#body_text
is schema:about of	named entity 'memory' named entity 'sampling' named entity 'Kolmogorov-Smirnov' named entity 'SARS-CoV-2' named entity 'skimmed milk' named entity 'peptides' named entity 'CD8 +' named entity 'cytokine' named entity 'humoral immunity' named entity 'peptides' named entity 'vaccine' named entity '28 days' named entity 'HIV' named entity 'epitope' named entity 'IFN-γ' named entity 'COVID' named entity 'human immunodeficiency viruses' named entity 'COVID' named entity 'infection' named entity 'epitope' named entity 'TNFα' named entity 'Mann-Whitney U test' named entity 'China'

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