AUTHOR=Bullen Georgia , Galson Jacob D. , Hall Gareth , Villar Pedro , Moreels Lien , Ledsgaard Line , Mattiuzzo Giada , Bentley Emma M. , Masters Edward W. , Tang David , Millett Sophie , Tongue Danielle , Brown Richard , Diamantopoulos Ioannis , Parthiban Kothai , Tebbutt Claire , Leah Rachael , Chaitanya Krishna , Ergueta-Carballo Sandra , Pazeraitis Deividas , Surade Sachin B. , Ashiru Omodele , Crippa Lucia , Cowan Richard , Bowler Matthew W. , Campbell Jamie I. , Lee Wing-Yiu Jason , Carr Mark D. , Matthews David , Pfeffer Paul , Hufton Simon E. , Sawmynaden Kovilen , Osbourn Jane , McCafferty John , Karatt-Vellatt Aneesh TITLE=Cross-Reactive SARS-CoV-2 Neutralizing Antibodies From Deep Mining of Early Patient Responses JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.678570 DOI=10.3389/fimmu.2021.678570 ISSN=1664-3224 ABSTRACT=

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.