Bavarian consortium for research on the pandemic disease COVID-19 (FOR-COVID)
Elucidate SARS-CoV-2 Antigenic escape Pathways resulting in immune Evasion (ESCAPE)
Prof. Dr. Oliver Keppler
Dr. Maximilian Münchhoff
Since its identification in December 2019 SARS-CoV-2 is constantly adapting to its new host
as illustrated by the emergence of variants with increased transmissibility and pathogenicity.
In this project we aim to characterise immune escape mutations that are selected under antibody and T-cell selection pressure. Building on our previous work we will use SARS-CoV-2 sequence analysis to identify potential immune escape mutations in vaccine breakthrough cases and patients with prolonged infection. Patient isolates will be tested for evasion of neutralising antibody responses and for replicative capacity in lung-derived cell models. Potential T cell escape mutations will be confirmed using samples of an already established clinical cohort of more than 300 HLA-typed COVID-19 patients. Epitope-specific T-cell responses will be characterised in depth by flowcytometry for phenotypic and functional properties. Using high-resolution sequencing of the T-cell receptor (TCR) beta chains we aim to identify antigen-specific common clonotypes and shared TCRs. Finally, we will investigate if confirmed escape mutations arose independently in multiple globally circulating lineages demonstrating convergent evolution in adaptation to the human immune system. ESCAPE will contribute to the molecular understanding of the evolving interaction of this pandemic virus with host immunity.
- Ludwig-Maximilians- Universität Munich (LMU Munich)