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A variant-proof monoclonal antibody (mAb) against SARS-CoV-2

Dr Harold Marcotte from the Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine of the Karolinksa Institutet focuses on passive immunization using Lactobacillus expressing antibody fragments against mucosal pathogens. Like many scientists, he leveraged his expertise and deployed new research projects at the onset of the COVID-19 pandemic, with a specific interest in monoclonal antibodies (mAbs). mAbs are molecules of choice in drug development due to their excellent specificity and safety. They are, however, also prone to viral escape (i.e. mutations in the virus can result in decreased activity). After a successful application to ISIDORe, Dr Marcotte teamed up with the Institute for Research in Biomedicine in Bellinzona to characterize mAbs derived from COVID-19-convalescent patients. Based on the results of inhibition studies, computational simulation, epitope mapping and kinetics studies, mAb 19n01 stood out for its ability to compete with ACE2 binding to the Receptor Binding Domain (RBD) of SARS-CoV-2 Spike protein and neutralize all SARS-CoV-2 variants it was tested against with nanomolar efficacy, making 19n01 a remarkably potent and broadly reactive mAb.