Wuhan, China is the epicenter of a rapidly spreading pandemic the World Health Organization (WHO) has officially designated as COVID-19. COVID-19 is caused by SARS-CoV-2, but how it is spread from person to person is still unclear. The asymptomatic presentation of the disease, and widespread travel out of Wuhan have permitted its rapid dissemination. As of March 16, 2020, there are over 175,000 cases affecting 162 countries with over 6,700 fatalities worldwide. SARS-CoV-2 is positive-sense RNA virus infecting vertebrate hosts that exists in a group of closely related co-evolving entities of which two others ? SARS-CoV and MERS-CoV ? have caused recent epidemics. Due to the complexity of anti-viral immunity, experience with other viruses has shown that swift success in vaccine development is by no means assured. A major challenge is the difficulty in adequately characterizing T cell-mediated recognition of viral epitopes. Finding the major shared specificities in COVID-19 subjects will help us understand what the most important CD4+ and CD8+ T cell responses will be. These findings can be deployed to determine the optimal vaccine formulation so as to elicit these T cell specificities. We hypothesize that T cell responses to specific epitopes of SARS-CoV-2 will be critical for its control in infected patients across diverse HLA haplotypes, and that a comprehensive mapping of epitopes recognized by those who clear the virus and their cognate TCRs will facilitate the development of the most effective vaccines for COVID-19 treatment. To pursue this hypothesis, we will employ some very new tools for T cell responses that have recently been developed at Stanford and the Princess Margaret Cancer Center, together with COVID-19 survivors? blood samples obtained in Toronto, Hong Kong and Stanford.

Public Health Relevance

COVID-19, caused by SARS-CoV-2, is now a worldwide pandemic and requires urgent and swift attention to develop efficacious therapeutics. Here we propose to use cutting-edge technologies developed in the Davis and Mak labs to comprehensively map viral epitopes and identify T cell targets critical for protection. Work here will directly inform ongoing vaccine development efforts and will be critical in halting the spread and mortality due to this virus.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Jiang, Chao
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Stanford University
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United States
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Sibener, Leah V; Fernandes, Ricardo A; Kolawole, Elizabeth M et al. (2018) Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding. Cell 174:672-687.e27
Ju, Chia-Hsin; Blum, Lisa K; Kongpachith, Sarah et al. (2018) Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains. Clin Immunol 193:70-79
Sweeney, Timothy E; Perumal, Thanneer M; Henao, Ricardo et al. (2018) A community approach to mortality prediction in sepsis via gene expression analysis. Nat Commun 9:694
Davis, Mark M; Tato, Cristina M (2018) Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Seeing the Forest Rather than a Few Trees. Cold Spring Harb Perspect Biol 10:
Gee, Marvin H; Han, Arnold; Lofgren, Shane M et al. (2018) Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes. Cell 172:549-563.e16
Keeffe, Jennifer R; Van Rompay, Koen K A; Olsen, Priscilla C et al. (2018) A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Rep 25:1385-1394.e7
Wagar, Lisa E; DiFazio, Robert M; Davis, Mark M (2018) Advanced model systems and tools for basic and translational human immunology. Genome Med 10:73
Good, Zinaida; Sarno, Jolanda; Jager, Astraea et al. (2018) Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nat Med 24:474-483
Satpathy, Ansuman T; Saligrama, Naresha; Buenrostro, Jason D et al. (2018) Transcript-indexed ATAC-seq for precision immune profiling. Nat Med 24:580-590
Vallania, Francesco; Tam, Andrew; Lofgren, Shane et al. (2018) Leveraging heterogeneity across multiple datasets increases cell-mixture deconvolution accuracy and reduces biological and technical biases. Nat Commun 9:4735

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