Influenza responses and repertoire in vaccination, infection and tonsil organoids.

Wuhan, China is the epicenter of a rapidly spreading pandemic the World Health Organization (WHO) hasofficially designated as COVID-19. COVID-19 is caused by SARS-CoV-2, but how it is spread from person toperson is still unclear. The asymptomatic presentation of the disease, and widespread travel out of Wuhan havepermitted its rapid dissemination. As of March 16, 2020, there are over 175,000 cases affecting 162 countrieswith over 6,700 fatalities worldwide. SARS-CoV-2 is positive-sense RNA virus infecting vertebrate hosts thatexists in a group of closely related co-evolving entities of which two others - SARS-CoV and MERS-CoV - havecaused recent epidemics. Due to the complexity of anti-viral immunity, experience with other viruses has shownthat swift success in vaccine development is by no means assured. A major challenge is the difficulty inadequately characterizing T cell-mediated recognition of viral epitopes. Finding the major shared specificities inCOVID-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 cellspecificities. We hypothesize that T cell responses to specific epitopes of SARS-CoV-2 will be critical forits control in infected patients across diverse HLA haplotypes, and that a comprehensive mapping ofepitopes recognized by those who clear the virus and their cognate TCRs will facilitate the developmentof the most effective vaccines for COVID-19 treatment. To pursue this hypothesis, we will employ some verynew tools for T cell responses that have recently been developed at Stanford and the Princess Margaret CancerCenter, together with COVID-19 survivors' blood samples obtained in Toronto, Hong Kong and Stanford.