Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.

ABSTRACT: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8⁺ T cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated. Evaluation of HLA class I stabilizing activity for 18 globally prevalent alleles identifies CD8⁺ T cell epitopes within highly networked regions with limited mutational frequenci

SUBMITTER: Nathan A 

PROVIDER: S-EPMC8241654 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature