Muenchhoff Lab - Research
SARS-CoV-2 evolution and immune evasion
Since its recent emergence SARS-CoV-2 is constantly evolving in adaptation to the human host. The development of SARS-CoV-2 variants-of-concern (VoCs) with substantially increased transmissibility and pathogenicity poses a major challenge for the control of the pandemic. Ongoing viral diversification reduces immunity elicited by currently available vaccines or prior infection.
In collaboration with our colleagues from the laboratory of Helmut Blum at the Gene Center, LMU Munich, we established a high-throughput pipeline for SARS-CoV-2 whole genome sequencing. Building on our previous work on the phylogenetic characterization of transmission chains and local outbreaks, we established a platform for genomic surveillance of SARS-CoV-2 teaming up with all other virological departments in Bavaria (https://www.bay-voc.lmu.de/). This network allows us to monitor in real time SARS-CoV-2 spread and the emergence/introduction of new variants on the population level. Beyond this, we are particularly interested in intra-host evolution of SARS-CoV-2 in adaption to selection pressure mediated by the adaptive immune system in patients with prolonged infection.
Selection of antibody and CD8 T-cell driven immune escape mutations in a SARS-CoV-2 infected immunocompromised host. In a patient who suffered persistent SARS-CoV-2 infection for 155 days until her death we observed the sequential emergence of immune escape mutations evading antibody and T-cell responses illustrating the plasticity of SARS-CoV-2 to evade adaptive immunity (https://www.nature.com/articles/s41467-022-32772-5).
We aim to characterize immune escape mutations that are selected under antibody and T-cell selection. Patient isolates are tested for evasion of neutralising antibody responses and for potential T-cell escape mutations. Epitope-specific T-cell responses are characterized 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 investigate if confirmed escape mutations arise independently in multiple globally circulating lineages demonstrating convergent evolution in adaptation to the human immune system.