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

Year of award: 2020

Grantholders

  • Prof Xiao-Ning Xu

    Imperial College London

  • Dr Nigel Temperton

    University of Kent

  • Dr Peter Kelleher

    Imperial College London

  • Prof Gavin Screaton

    University of Oxford

  • Prof Honglin Chen

    University of Hong Kong

  • Prof Kwok Yung Yuen

    University of Hong Kong

  • Prof Zhiwei Chen

    University of Hong Kong

Project summary

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. Fatality rates are up to 10% in elderly patients. 

Almost 100% of patients show bilateral patchy shadows or ground glass opacity in their lungs in 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. 

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 and up-to-date lab technologies to ensure the feasibility of this study.

Our goals are to: 

  1. define SARS-CoV-2 specific serum profiles (epitopes) using a yeast display antigen library
  2. determine antibody functions including antibody-dependent enhancement (ADE) versus neutralising activities in vitro assays
  3. study T cell (CD4 and CD8) responses to the whole SARS-CoV-2 genome
  4. evaluate ALI in response to live SARS-CoV-2 infection with or without passive immunity (antibody or T cells) generated from vaccine candidates in a humanised mice model.