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Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

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Title: Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts
Authors: Kundu, R
Sam Narean, J
Wang, L
Fenn, J
Pillay, T
Derqui, N
Conibear, E
Koycheva, A
Davies, M
Tolosa-Wright, M
Hakki, S
Varro, R
McDermott, E
Hammett, S
Cutajar, J
Thwaites, R
Parker, E
Rosados, C
McClure, M
Tedder, R
Taylor, G
Dunning, J
Lalvani, A
Item Type: Journal Article
Abstract: Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p=0.0139), and nucleocapsid-specific (p=0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n=26), when compared with those who convert to PCR-positive (n=26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
Date of Acceptance: 1-Dec-2021
URI: http://hdl.handle.net/10044/1/93018
DOI: 10.1038/s41467-021-27674-x
ISSN: 2041-1723
Publisher: Nature Research
Journal / Book Title: Nature Communications
Volume: 13
Copyright Statement: © The Author(s) 2022
Sponsor/Funder: Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: MR/R021643/1
NIHR200927
Publication Status: Published
Article Number: 80
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine



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