Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.
Cell
; 184(17): 4401-4413.e10, 2021 08 19.
Article
in En
| MEDLINE
| ID: mdl-34265281
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 frequencies in circulating SARS-CoV-2 variants and deep-sequenced primary isolates. Moreover, these epitopes elicit demonstrable CD8+ T cell reactivity in convalescent individuals but reduced recognition in recipients of mRNA-based vaccines. These data thereby elucidate key mutationally constrained regions and immunogenic epitopes in the SARS-CoV-2 proteome for a global T-cell-based vaccine against emerging variants and SARS-like coronaviruses.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epitopes, T-Lymphocyte
/
COVID-19 Vaccines
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2021
Document type:
Article
Affiliation country:
United States