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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI057229-17S1
Application #
10142952
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Jiang, Chao
Project Start
2020-05-19
Project End
2022-03-31
Budget Start
2020-05-19
Budget End
2021-03-31
Support Year
17
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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