A comprehensive study of immunopathogenesis of SARS-CoV-2 infection'

Since December 2019 the emergence of severe acute respiratory infections (COVID-19) in China, caused by the new coronavirus SARS-CoV-2, has posed a huge threat to global health with fatality rates up to 10% in elderly patients. Almost 100% of patients showed bilateral patchy shadows or ground glass opacity in their lungs by chest CT scans indicating acute lung injury (ALI). Therefore, understanding the underlying mechanism(s) of ALI induced by SARS-CoV-2 is very important to inform vaccine safety and immunotherapeutic strategies. In this proposal, we will investigate the host immune responses and their association with severity of ALI in patient samples and animal models. We will bring together a team of experts with complementary expertise including immunopathology in coronavirus infections, up-to-date lab technologies, and know-how to ensure the feasibility of this study with the following goals: 1) defining SARS-CoV-2 specific serum profiles (epitopes) using yeast display antigen library 2) determining antibody functions including antibody-dependent enhancement (ADE) vs neutralizing activities in vitro assays 3) studying T cell (CD4 and CD8) responses to whole SARS-CoV-2 genome 4) evaluating ALI in response to live SARS-CoV-2 infection with or without passive immunity (antibody or T cells) generated from vaccine candidates in a humanized mice model.