Journal Article

Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster

Hansen, Randi Westh, Barnkob, Nanna Møller, Vuillard, Laurent-Michel, Juhl, Anna Karina, Schleimann, Mariane Høgsbjerg, Rothemejer, Frederik Holm, Koefoed, Klaus, Georges, Amédée Des, Bansia, Harsh, Vestergaard, Mike, Worsaae, Anne, Pedersen, Maria Lange, Brown, Deijona, Lende, Stine Sofie Frank, Østergaard, Lars, Tolstrup, Martin, Gjetting, Torben, Rahimic, Anna Halling Folkmar

2023

Overview

Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo . The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACE2 / Angiotensin-converting enzyme 2 / Antibodies / Antigens / Binders / Binding / Biology and life sciences / Clusters / COVID-19 / COVID-19 vaccines / Effectiveness / Epitopes / Genes / Immunization / Lymphocytes B / Medicine and health sciences / Monoclonal antibodies / Mutation / Neutralization / Neutralizing / Pandemics / Population / Research and Analysis Methods / Severe acute respiratory syndrome coronavirus 2 / Structural analysis / Transcription factors / Transcriptomics / Vaccines / Viral diseases / Viruses