@article {1608576,
	title = {Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses},
	journal = {Cell},
	volume = {184},
	number = {17},
	year = {2021},
	month = {2021 08 19},
	pages = {4401-4413.e10},
	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\&nbsp;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\&nbsp;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\&nbsp;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.},
	keywords = {CD8-Positive T-Lymphocytes, COVID-19, COVID-19 Vaccines, Epitopes, T-Lymphocyte, HLA Antigens, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2021.06.029},
	author = {Nathan, Anusha and Rossin, Elizabeth J and Kaseke, Clarety and Park, Ryan J and Khatri, Ashok and Koundakjian, Dylan and Urbach, Jonathan M and Singh, Nishant K and Bashirova, Arman and Tano-Menka, Rhoda and Senjobe, Fernando and Waring, Michael T and Piechocka-Trocha, Alicja and Garcia-Beltran, Wilfredo F and Iafrate, A John and Naranbhai, Vivek and Carrington, Mary and Walker, Bruce D and Gaiha, Gaurav D}
}
