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S. Meyer, I. Blaas, R. C. Bollineni, Marina Delić-Šarac, T. Tran, C. Knetter, Ke-Zheng Dai, T. Madssen, J. Vaage, A. Gustavsen, Weiwen Yang, L. S. Nissen-Meyer, Karolos Douvlataniotis, Maarja Laos, M. Nielsen, B. Thiede, Arne Søraas, F. Lund-Johansen, E. Rustad, J. Olweus
1 2021.

Public T-cell epitopes shared among SARS-CoV-2 variants are presented on prevalent HLA class I alleles

T-cell epitopes with broad population coverage may form the basis for a new generation of SARS-CoV-2 vaccines. However, published studies on immunoprevalence are limited by small test cohorts, low frequencies of antigen-specific cells and lack of data correlating eluted HLA ligands with T-cell responsiveness. As the protective role of pre-existing cross-reactivity to homologous peptides is unclear, we aimed to identify SARS-CoV-2-specific minimal epitopes recognized by CD8 T-cells among 48 peptides eluted from prevalent HLA alleles, and an additional 84 predicted binders, in a large cohort of convalescents (n=83) and pre-pandemic control samples (n=19). We identified nine conserved SARS-CoV-2-specific epitopes restricted by four of the most prevalent HLA class I alleles in the Norwegian study cohort, to which responding CD8 T cells were detected in 70-100% of convalescents expressing the relevant HLA allele. Only two of these were derived from the Spike protein, included in current vaccines. We found a strong correlation between immunoprevalence and immunodominance. Thus, the CD8 T-cell response to SARS-CoV-2 is more focused than previously believed. Using a new algorithm, we predict that a vaccine including these epitopes could induce a T-cell response in 83% of Caucasians.


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