Characterisation of the Immune Response to SARS-CoV-2 / COVID-19

AIMS AND OBJECTIVES The objective of this project is to understand the host immune response to infection with SARS-CoV-2 over time in convalescent adults, including acquired immune responses, gene expression profiling in peripheral blood and to identify host genetic variants associated with disease progressions or severity. We would like to ascertain why different people experience different disease phenotypes with this coronavirus infection. Our primary objective is to determine key protective cellular immune parameters (e.g. T cell responses) and confirm whether there are host genetic factors that provide protection from disease. We aim to define immunodominant SARS-CoV-2 T-cell epitopes by screening overlapping peptides from the viral proteome and mapping responses to individual COVID proteins expressed intracellularly in antigen-presenting cells (to confirm processing and presentation at the cell surface). Peptide-HLA multimers will be constructed for confirmed immunodominant responses. These reagents will allow rapid enumeration and tracking of COVID-specific T cell responses in patient samples. Our secondary objective is to determine whether there are public (shared) T-cell receptor responses to SARS-CoV-2. We will also examine whether pre-existing T-cells responses to other viruses protect against SARS-CoV-2-induced disease (COVID-19). T-cells generated will be used to test and verify detection reagents. These reagents will be developed for various projects in Oxford University including monitoring of T-cell responses induced by COVID vaccines. We will also establish whether pre-existing cross-reactive immunity to other coronaviruses correlates with disease severity as seen with the 2009 swine flu pandemic.