Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.
- Resource Type
- Article
- Authors
- Nathan, Anusha; Rossin, Elizabeth J.; Kaseke, Clarety; Park, Ryan J.; Khatri, Ashok; Koundakjian, Dylan; Urbach, Jonathan M.; Singh, Nishant K.; Bashirova, Arman; Tano-Menka, Rhoda; Senjobe, Fernando; Waring, Michael T.; Piechocka-Trocha, Alicja; Garcia-Beltran, Wilfredo F.; Iafrate, A. John; Naranbhai, Vivek; Carrington, Mary; Walker, Bruce D.; Gaiha, Gaurav D.
- Source
- Cell. Aug2021, Vol. 184 Issue 17, p4401-4401. 1p.
- Subject
- *T cells
*SARS-CoV-2
*COVID-19
*VACCINES
- Language
- ISSN
- 0092-8674
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. [Display omitted] • Structure-based network analysis identifies mutation-constrained residues in SARS-CoV-2 • Highly networked residues are conserved across SARS-CoV-2 variants and sarbecoviruses • HLA stabilization defines highly networked epitopes with limited variation in VOCs • Highly networked epitopes elicit CD8+ T cell reactivity in recovered individuals Structure-based network analyses identify regions in the SARS-CoV-2 proteome that are mutationally constrained and bear CD8+ T cell epitopes that are also conserved in emerging variants as well as other sarbecoviruses. These epitopes elicit stronger CD8+ T cell responses in convalescent individuals over mRNA vaccine recipients and provide a framework for a broad T-cell-based vaccine against coronaviruses. [ABSTRACT FROM AUTHOR]