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Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence

Georgia Bullen, Jacob D. Galson, Pedro Villar, Lien Moreels, Line Ledsgaard, Giada Mattiuzzo, Gareth Hall, Emma M. Bentley, Edward W. Masters, David Tang, Sophie Millett, Danielle Tongue, Richard Brown, Ioannis Diamantopoulos, Kothai Parthiban, Claire Tebbutt, Rachael Leah, Krishna Chaitanya, Deividas Pazeraitis, Sachin B. Surade, Omodele Ashiru, Lucia Crippa, Richard Cowan, View ORCID ProfileMatthew W. Bowler, Jamie I. Campbell, Wing-Yiu Jason Lee, Mark D. Carr, David Matthews, Paul Pfeffer, Simon E. Hufton, Kovilen Sawmynaden, Jane Osbourn, John McCafferty, View ORCID ProfileAneesh Karatt-Vellatt
doi: https://doi.org/10.1101/2020.12.29.424711
Georgia Bullen
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Jacob D. Galson
2Alchemab Therapeutics Ltd., 55-56 Russell Square, London, WC1B 4HP, United Kingdom
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Pedro Villar
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Lien Moreels
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Line Ledsgaard
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Giada Mattiuzzo
3National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, United Kingdom
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Gareth Hall
4Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, University Road, Leicester, LE1 7RH, United Kingdom
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Emma M. Bentley
3National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, United Kingdom
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Edward W. Masters
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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David Tang
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Sophie Millett
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Danielle Tongue
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Richard Brown
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Ioannis Diamantopoulos
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Kothai Parthiban
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Claire Tebbutt
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Rachael Leah
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Krishna Chaitanya
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Deividas Pazeraitis
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Sachin B. Surade
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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Omodele Ashiru
6Abcam, Discovery Drive, Cambridge Biomedical Campus, Cambridgeshire, CB2 0AX, United Kingdom
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Lucia Crippa
6Abcam, Discovery Drive, Cambridge Biomedical Campus, Cambridgeshire, CB2 0AX, United Kingdom
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Richard Cowan
4Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, University Road, Leicester, LE1 7RH, United Kingdom
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Matthew W. Bowler
7European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France
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  • ORCID record for Matthew W. Bowler
Jamie I. Campbell
6Abcam, Discovery Drive, Cambridge Biomedical Campus, Cambridgeshire, CB2 0AX, United Kingdom
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Wing-Yiu Jason Lee
8Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AD, United Kingdom
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Mark D. Carr
4Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, University Road, Leicester, LE1 7RH, United Kingdom
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David Matthews
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Paul Pfeffer
8Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AD, United Kingdom
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Simon E. Hufton
3National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, United Kingdom
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Kovilen Sawmynaden
5LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, United Kingdom
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Jane Osbourn
2Alchemab Therapeutics Ltd., 55-56 Russell Square, London, WC1B 4HP, United Kingdom
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John McCafferty
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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  • For correspondence: akv@maxion.co.uk jmc@iontas.co.uk
Aneesh Karatt-Vellatt
1IONTAS Ltd., Iconix Park, London, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom
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  • ORCID record for Aneesh Karatt-Vellatt
  • For correspondence: akv@maxion.co.uk jmc@iontas.co.uk
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Abstract

Passive immunisation using monoclonal antibodies will play a vital role in the fight against COVID-19. Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase. Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported. The study highlighted the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection. Furthermore, we highlight a highly convergent antibody response with the same sequences occurring both within this study group and also within the responses described in previously published anti-SARS-CoV-2 studies.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 29, 2020.
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Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence
Georgia Bullen, Jacob D. Galson, Pedro Villar, Lien Moreels, Line Ledsgaard, Giada Mattiuzzo, Gareth Hall, Emma M. Bentley, Edward W. Masters, David Tang, Sophie Millett, Danielle Tongue, Richard Brown, Ioannis Diamantopoulos, Kothai Parthiban, Claire Tebbutt, Rachael Leah, Krishna Chaitanya, Deividas Pazeraitis, Sachin B. Surade, Omodele Ashiru, Lucia Crippa, Richard Cowan, Matthew W. Bowler, Jamie I. Campbell, Wing-Yiu Jason Lee, Mark D. Carr, David Matthews, Paul Pfeffer, Simon E. Hufton, Kovilen Sawmynaden, Jane Osbourn, John McCafferty, Aneesh Karatt-Vellatt
bioRxiv 2020.12.29.424711; doi: https://doi.org/10.1101/2020.12.29.424711
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Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence
Georgia Bullen, Jacob D. Galson, Pedro Villar, Lien Moreels, Line Ledsgaard, Giada Mattiuzzo, Gareth Hall, Emma M. Bentley, Edward W. Masters, David Tang, Sophie Millett, Danielle Tongue, Richard Brown, Ioannis Diamantopoulos, Kothai Parthiban, Claire Tebbutt, Rachael Leah, Krishna Chaitanya, Deividas Pazeraitis, Sachin B. Surade, Omodele Ashiru, Lucia Crippa, Richard Cowan, Matthew W. Bowler, Jamie I. Campbell, Wing-Yiu Jason Lee, Mark D. Carr, David Matthews, Paul Pfeffer, Simon E. Hufton, Kovilen Sawmynaden, Jane Osbourn, John McCafferty, Aneesh Karatt-Vellatt
bioRxiv 2020.12.29.424711; doi: https://doi.org/10.1101/2020.12.29.424711

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