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

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-27674-x

2041-1723

Rhia Kundu, Janakan Sam Narean, Lulu Wang, Joe Fenn, Timesh D Pillay, Nieves Derqui, 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 O. McClure, Richard S. Tedder, Graham P. Taylor, Jake Dunning, Ajit Lalvani,

vaccines and immunoinformatics approaches

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.