Beyond Spike: Identification of nine highly prevalent SARS-CoV-2-specific CD8 T-cell epitopes in a large Norwegian cohort

Abstract

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. Here, we investigate CD8 T-cell responses to 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 identify nine conserved SARS-CoV-2 specific epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians, to which responding CD8 T cells are detected in 70-100% of convalescents expressing the relevant HLA allele, including two novel epitopes. We find a strong correlation between immunoprevalence and immunodominance. Using a new algorithm, we predict that a vaccine including these epitopes would induce a T cell response in 83% of Caucasians. Significance Statement: Vaccines that induce broad T-cell responses may boost immunity as protection from current vaccines against SARS-CoV-2 is waning. From a manufacturing standpoint, and to deliver the highest possible dose of the most immunogenic antigens, it is rational to limit the number of epitopes to those inducing the strongest immune responses in the highest proportion of individuals in a population. Our data show that the CD8 T cell response to SARS-CoV-2 is more focused than previously believed. We identify nine conserved SARS-CoV-2 specific CD8 T cell epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians and demonstrate that seven of these are endogenously presented.

Can B cell‐deficient patients rely on COVID‐19 vaccine‐induced T‐cell immunity?

“…Riise et al 15 applied a different approach. They evaluated vaccine‐induced CD8 T cell responses to defined immunogenic spike epitopes identified in convalescent patients 16 and quantified responding cells using fluorescently tagged peptide‐bound HLA multimers. This bypassed the need for peptide antigen presentation by autologous cells present in the patients’ blood, which may be deficient in number or quality, and directly evaluated whether a T cell response had been generated, although did not provide evidence of T‐cell functionality.…”