Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA; Corresponding author
Da-Yuan Chen
Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA
Siranush Sarkizova
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Hannah B. Taylor
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Matteo Gentili
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Gabrielle M. Hernandez
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Leah R. Pearlman
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Matthew R. Bauer
Harvard Program in Biological and Biomedical Sciences, Division of Medical Sciences, Harvard University Medical School, Boston, MA, USA
Charles M. Rice
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA
Karl R. Clauser
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Nir Hacohen
Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA
Steven A. Carr
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Jennifer G. Abelin
Broad Institute of MIT and Harvard University, Cambridge, MA, USA
Mohsan Saeed
Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA
Pardis C. Sabeti
Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
Summary: Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4+ T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize vaccine effectiveness.
