A comprehensive study of immunopathogenesis of SARS-CoV-2 infection (360G-Wellcome-220981_Z_20_Z)

£864,564

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.

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Grant Details

Amount Awarded 864564
Applicant Surname Xu
Approval Committee Epidemic Technical Advisory Panel
Award Date 2020-09-30T00:00:00+00:00
Financial Year 2019/20
Grant Programme: Title Coronavirus
Internal ID 220981/Z/20/Z
Lead Applicant Prof Xiao-Ning Xu
Other Applicant(s) Dr Nigel Temperton, Dr Peter Kelleher, Prof Gavin Screaton, Prof Honglin Chen, Prof Kwok Yung Yuen, Prof Zhiwei Chen
Partnership Name Wellcome-DFID Epidemic Preparedness
Partnership Value 864564
Planned Dates: End Date 2023-11-03T00:00:00+00:00
Planned Dates: Start Date 2020-08-04T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London