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 and Ajit Lalvani
Additional contact information
Rhia Kundu: Imperial College London
Janakan Sam Narean: Imperial College London
Lulu Wang: Imperial College London
Joseph Fenn: Imperial College London
Timesh Pillay: Imperial College London
Nieves Derqui Fernandez: Imperial College London
Emily Conibear: Imperial College London
Aleksandra Koycheva: Imperial College London
Megan Davies: Imperial College London
Mica Tolosa-Wright: Imperial College London
Seran Hakki: Imperial College London
Robert Varro: Imperial College London
Eimear McDermott: Imperial College London
Sarah Hammett: Imperial College London
Jessica Cutajar: Imperial College London
Ryan S. Thwaites: Imperial College London
Eleanor Parker: Imperial College London
Carolina Rosadas: Imperial College London
Myra McClure: Imperial College London
Richard Tedder: Imperial College London
Graham P. Taylor: Imperial College London
Jake Dunning: National Infection Service, Public Health England
Ajit Lalvani: Imperial College London

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: 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: 2022
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Citations: View citations in EconPapers (13)

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DOI: 10.1038/s41467-021-27674-x

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