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

Rhia Kundu; Janakan Sam Narean; Lulu Wang; Joseph Fenn; Timesh Pillay; Nieves Derqui Fernandez; Emily Conibear; Aleksandra Koycheva; Megan Davies; Mica Tolosa-Wright; Seran Hakki; Robert Varro; Eimear McDermott; Sarah Hammett; Jessica Cutajar; Ryan S Thwaites; Eleanor Parker; Carolina Rosadas; Myra McClure; Richard Tedder; Graham P Taylor; Jake Dunning; Ajit Lalvani

doi:10.1038/s41467-021-27674-x

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

Rhia Kundu, Janakan Sam Narean, Lulu Wang, Joseph Fenn, Timesh Pillay, Nieves Derqui Fernandez, Emily Conibear, Aleksandra Koycheva, Megan Davies, Mica Tolosa-Wright, Seran Hakki, Robert Varro, Eimear McDermott, Sarah Hammett, Jessica Cutajar, Ryan S Thwaites, Eleanor Parker, Carolina Rosadas, Myra McClure, Richard TedderGraham P Taylor, Jake Dunning, Ajit Lalvani

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

202 Citations (Scopus)

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.

Original language	English
Article number	80
Pages (from-to)	80
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27674-x
Publication status	Published - 10 Jan 2022

Keywords

Adult
Antibodies, Viral/immunology
COVID-19/epidemiology
Contact Tracing/methods
Coronavirus/immunology
Cross Reactions/immunology
Epitopes, T-Lymphocyte/immunology
Female
Humans
Male
Memory T Cells/immunology
Middle Aged
Pandemics/prevention & control
SARS-CoV-2/genetics
Spike Glycoprotein, Coronavirus/genetics
Viral Proteins/genetics
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-021-27674-x

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Kundu, R., Narean, J. S., Wang, L., Fenn, J., Pillay, T., Fernandez, N. D., Conibear, E., Koycheva, A., Davies, M., Tolosa-Wright, M., Hakki, S., Varro, R., McDermott, E., Hammett, S., Cutajar, J., Thwaites, R. S., Parker, E., Rosadas, C., McClure, M., ... Lalvani, A. (2022). Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nature Communications, 13(1), 80. Article 80. https://doi.org/10.1038/s41467-021-27674-x

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

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-na{\"i}ve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.",

keywords = "Adult, Antibodies, Viral/immunology, COVID-19/epidemiology, Contact Tracing/methods, Coronavirus/immunology, Cross Reactions/immunology, Epitopes, T-Lymphocyte/immunology, Female, Humans, Male, Memory T Cells/immunology, Middle Aged, Pandemics/prevention & control, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/genetics, Viral Proteins/genetics, Young Adult",

author = "Rhia Kundu and Narean, {Janakan Sam} and Lulu Wang and Joseph Fenn and Timesh Pillay and Fernandez, {Nieves Derqui} and Emily Conibear and Aleksandra Koycheva and Megan Davies and Mica Tolosa-Wright and Seran Hakki and Robert Varro and Eimear McDermott and Sarah Hammett and Jessica Cutajar and Thwaites, {Ryan S} and Eleanor Parker and Carolina Rosadas and Myra McClure and Richard Tedder and Taylor, {Graham P} and Jake Dunning and Ajit Lalvani",

note = "Funding Information: We would like to thank all our participants for letting us into their homes during difficult times to contribute to this research. We would also like to acknowledge PHE data scientists for their assistance with identifying potential participants, and the team at base station for providing essential support to the research nurses. We thank Prof Peter Beverley, Dr Elma Tchilian, Prof Charles Bangham, and Dr John Tregoning for their feedback on the manuscript. This study is supported by the National Institute for Health Research (NIHR), Grant number NIHR 200927 (A.L.) and the Medical Research Council, grant number MR/R021643/1 (A.L.). The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or the Medical Research Council. This work was also supported by the Imperial COVID Fund (R.K.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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month = jan,

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doi = "10.1038/s41467-021-27674-x",

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Kundu, R, Narean, JS, Wang, L, Fenn, J, Pillay, T, Fernandez, ND, Conibear, E, Koycheva, A, Davies, M, Tolosa-Wright, M, Hakki, S, Varro, R, McDermott, E, Hammett, S, Cutajar, J, Thwaites, RS, Parker, E, Rosadas, C, McClure, M, Tedder, R, Taylor, GP, Dunning, J & Lalvani, A 2022, 'Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts', Nature Communications, vol. 13, no. 1, 80, pp. 80. https://doi.org/10.1038/s41467-021-27674-x

TY - JOUR

T1 - Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

AU - Kundu, Rhia

AU - Narean, Janakan Sam

AU - Wang, Lulu

AU - Fenn, Joseph

AU - Pillay, Timesh

AU - Fernandez, Nieves Derqui

AU - Conibear, Emily

AU - Koycheva, Aleksandra

AU - Davies, Megan

AU - Tolosa-Wright, Mica

AU - Hakki, Seran

AU - Varro, Robert

AU - McDermott, Eimear

AU - Hammett, Sarah

AU - Cutajar, Jessica

AU - Thwaites, Ryan S

AU - Parker, Eleanor

AU - Rosadas, Carolina

AU - McClure, Myra

AU - Tedder, Richard

AU - Taylor, Graham P

AU - Dunning, Jake

AU - Lalvani, Ajit

N1 - Funding Information: We would like to thank all our participants for letting us into their homes during difficult times to contribute to this research. We would also like to acknowledge PHE data scientists for their assistance with identifying potential participants, and the team at base station for providing essential support to the research nurses. We thank Prof Peter Beverley, Dr Elma Tchilian, Prof Charles Bangham, and Dr John Tregoning for their feedback on the manuscript. This study is supported by the National Institute for Health Research (NIHR), Grant number NIHR 200927 (A.L.) and the Medical Research Council, grant number MR/R021643/1 (A.L.). The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or the Medical Research Council. This work was also supported by the Imperial COVID Fund (R.K.). Publisher Copyright: © 2022, The Author(s).

PY - 2022/1/10

Y1 - 2022/1/10

N2 - 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.

AB - 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.

KW - Adult

KW - Antibodies, Viral/immunology

KW - COVID-19/epidemiology

KW - Contact Tracing/methods

KW - Coronavirus/immunology

KW - Cross Reactions/immunology

KW - Epitopes, T-Lymphocyte/immunology

KW - Female

KW - Humans

KW - Male

KW - Memory T Cells/immunology

KW - Middle Aged

KW - Pandemics/prevention & control

KW - SARS-CoV-2/genetics

KW - Spike Glycoprotein, Coronavirus/genetics

KW - Viral Proteins/genetics

KW - Young Adult

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U2 - 10.1038/s41467-021-27674-x

DO - 10.1038/s41467-021-27674-x

M3 - Article

C2 - 35013199

SN - 2041-1723

VL - 13

SP - 80

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 80

ER -

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

Abstract

Keywords

UN SDGs

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