High levels of T-cells from common cold coronaviruses can provide protection against COVID-19, an Imperial College London study has found, which could inform approaches for second- generation vaccines.
Immunity against COVID-19 is a complex picture, and while there is evidence of waning antibody levels six months after vaccination, T-cells are also believed to play a vital role in providing protection.
The study, which began in September 2020, looked at levels of cross-reactive T-cells generated by previous common colds in 52 household contacts of positive COVID-19 cases shortly after exposure, to see if they went on to develop infection.
It found that the 26 who did not develop infection had significantly higher levels of those T-cells than people who did get infected. Imperial did not say how long protection from the T-cells would last.
“We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection,” study author Dr Rhia Kundu said.
The research, published in Nature Communications, said that the internal proteins of the SARS-CoV-2 virus, which are targeted by the T-cells, could offer an alternative target for vaccine makers.
Current COVID-19 vaccines target the spike protein, which mutates regularly, creating variants such as Omicron that lessen the efficacy of vaccines against symptomatic infection.
“In contrast, the internal proteins targeted by the protective T-cells we identified mutate much less,” Professor Ajit Lalvani, co-author, said.
“Consequently, they are highly conserved between the various SARS- CoV-2 variants, including Omicron. New vaccines that include these conserved, internal proteins would therefore induce broadly protective T cell responses that should protect against current and future SARS-CoV-2 variants.”
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.
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.
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