Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients
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..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 19. März Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peng, Yanchun [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/2020.06.05.134551 |
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| PPN (Katalog-ID): |
XBI018086470 |
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| 520 | |a 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. | ||
| 700 | 1 | |a Mentzer, Alexander J. |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Guihai |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Zixi |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Danning |e verfasserin |4 aut | |
| 700 | 1 | |a Dejnirattisai, Wanwisa |e verfasserin |4 aut | |
| 700 | 1 | |a Rostron, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Supasa, Piyada |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Lopez-Camacho, Cesar |e verfasserin |4 aut | |
| 700 | 1 | |a Slon-campos, Jose |e verfasserin |4 aut | |
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| 700 | 1 | |a Grimes, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Antson, Fred |e verfasserin |4 aut | |
| 700 | 1 | |a Bayfield, Oliver W. |e verfasserin |4 aut | |
| 700 | 1 | |a Hawkins, Dorothy EDP. |e verfasserin |4 aut | |
| 700 | 1 | |a Ker, De-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Turtle, Lance |e verfasserin |4 aut | |
| 700 | 1 | |a Subramaniam, Krishanthi |e verfasserin |4 aut | |
| 700 | 1 | |a Thomson, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Dold, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Ratcliff, Jeremy |e verfasserin |4 aut | |
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