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  https://doi.org/10.1038/s41467-021-27674-x

• PDF: https://www.nature.com/articles/s41467-021-27674-x.pdf

• 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.

• https://www.nature.com/articles/s41467-021-27674-x