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

  1. Author:
    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

  2. Author Address

    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., The Broad Institute, Cambridge, MA 02142, USA; Harvard Medical School Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Harvard Radiation Oncology Program, Boston, MA 02114, USA., Massachusetts General Hospital Endocrine Division and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02142, USA., Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, MA 02115, USA., 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., 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., 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 Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., 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.,
    1. Year: 2021
    2. Date: Aug 19
    3. Epub Date: 2021 06 30
  2. Journal: Cell
    1. 184
    2. 17
    3. Pages: 4401-4413.e10
  4. Type of Article: Article
  5. ISSN: 0092-8674
  1. 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. Copyright © 2021 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2021.06.029
  3. PMID: 34265281
  4. View record in Web of Science®
  5. WOS: 000686554600006
  6. PII : S0092-8674(21)00797-2

Library Notes

  1. Fiscal Year: FY2020-2021
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