
There is a more recent version of this eprint available. Click here to view it.
Peng, Y., Mentzer, A.J., Liu, G. et al. (57 more authors) (Submitted: 2020) Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients. [Preprint - bioRxiv] (Submitted)
Abstract
<jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup>and/or CD8<jats:sup>+</jats:sup>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<jats:sup>+</jats:sup>T cells than spike-specific CD8<jats:sup>+</jats:sup>T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8<jats:sup>+</jats:sup>to CD4<jats:sup>+</jats:sup>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.</jats:p>
Metadata
Item Type: | Preprint |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2020 The Author(s). For reuse permissions, please contact the Author(s). |
Keywords: | Pneumonia & Influenza; Prevention; Biodefense; Immunization; Infectious Diseases; Vaccine Related; Emerging Infectious Diseases; Biological and endogenous factors; Aetiology; Infection; Good Health and Well Being |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 May 2023 15:45 |
Last Modified: | 05 May 2023 15:45 |
Published Version: | http://dx.doi.org/10.1101/2020.06.05.134551 |
Status: | Submitted |
Publisher: | Cold Spring Harbor Laboratory |
Identification Number: | 10.1101/2020.06.05.134551 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:198948 |
Available Versions of this Item
- Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients. (deposited 05 May 2023 15:45) [Currently Displayed]