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Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.
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.
  • Nathan A; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA.
  • Rossin EJ; The Broad Institute, Cambridge, MA 02142, USA; Harvard Medical School Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA.
  • Kaseke C; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Park RJ; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Harvard Radiation Oncology Program, Boston, MA 02114, USA.
  • Khatri A; Massachusetts General Hospital Endocrine Division and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Koundakjian D; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Urbach JM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Singh NK; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02142, USA.
  • Bashirova A; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
  • Tano-Menka R; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Senjobe F; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
  • Waring MT; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Piechocka-Trocha A; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Garcia-Beltran WF; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, MA 02115, USA.
  • Iafrate AJ; Department of Pathology, Massachusetts General Hospital, MA 02115, USA.
  • Naranbhai V; Department of Medicine, Massachusetts General Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa.
  • Carrington M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
  • Walker BD; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; The Broad Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa; Institute for Medical Engineering and S
  • Gaiha GD; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: ggaiha@mgh.harvard.edu.
Cell ; 184(17): 4401-4413.e10, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1293638
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epitopes, T-Lymphocyte / COVID-19 Vaccines Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.06.029

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epitopes, T-Lymphocyte / COVID-19 Vaccines Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.06.029