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Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures

Jacob D. Galson, Sebastian Schaetzle, Rachael J. M. Bashford-Rogers, Matthew I. J. Raybould, Aleksandr Kovaltsuk, Gavin J. Kilpatrick, Ralph Minter, Donna K. Finch, Jorge Dias, Louisa James, Gavin Thomas, Wing-Yiu Jason Lee, Jason Betley, Olivia Cavlan, Alex Leech, View ORCID ProfileCharlotte M. Deane, Joan Seoane, Carlos Caldas, Dan Pennington, Paul Pfeffer, Jane Osbourn
doi: https://doi.org/10.1101/2020.05.20.106294
Jacob D. Galson
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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  • For correspondence: jake@alchemab.com jane@alchemab.com
Sebastian Schaetzle
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Rachael J. M. Bashford-Rogers
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
2Wellcome Centre for Human Genetics, Roosevelt Dr, Oxford, OX3 7BN, UK
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Matthew I. J. Raybould
3Oxford Protein Informatics Group, Department of Statistics, University of Oxford, Oxford OX1 3LB, UK
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Aleksandr Kovaltsuk
3Oxford Protein Informatics Group, Department of Statistics, University of Oxford, Oxford OX1 3LB, UK
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Gavin J. Kilpatrick
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Ralph Minter
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Donna K. Finch
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Jorge Dias
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Louisa James
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
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Gavin Thomas
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
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Wing-Yiu Jason Lee
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
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Jason Betley
5Illumina, Inc., Illumina Centre, Granta Park, Cambridge CB21 6DF, UK
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Olivia Cavlan
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Alex Leech
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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Charlotte M. Deane
3Oxford Protein Informatics Group, Department of Statistics, University of Oxford, Oxford OX1 3LB, UK
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  • ORCID record for Charlotte M. Deane
Joan Seoane
6Translational Research Program, Vall d’Hebron Institute of Oncology, Barcelona 08035, Spain
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Carlos Caldas
7Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK
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Dan Pennington
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
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Paul Pfeffer
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK
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Jane Osbourn
1Alchemab Therapeutics Ltd, 55-56 Russell Square, London, WC1B 4HP, UK
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  • For correspondence: jake@alchemab.com jane@alchemab.com
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Abstract

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 19 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients and may be a positive indicator of disease outcome. Clonal expansion of the B cell memory response is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 777 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralising antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand and predict positive patient responses.

Competing Interest Statement

JO, AL, OC, SS, JDG, JD, RM and DKF are employees of Alchemab Therapeutics Limited. RJMB-R is a founder of and consultant to Alchemab Therapeutics Limited. GJK is a consultant to Alchemab Therapeutics Limited. CC is a member of the AstraZeneca External Science Panel and has research grants from Roche, Genentech, AstraZeneca, and Servier that are administered by the University of Cambridge.

Copyright 
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 4.0 International license.
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Posted May 20, 2020.
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Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures
Jacob D. Galson, Sebastian Schaetzle, Rachael J. M. Bashford-Rogers, Matthew I. J. Raybould, Aleksandr Kovaltsuk, Gavin J. Kilpatrick, Ralph Minter, Donna K. Finch, Jorge Dias, Louisa James, Gavin Thomas, Wing-Yiu Jason Lee, Jason Betley, Olivia Cavlan, Alex Leech, Charlotte M. Deane, Joan Seoane, Carlos Caldas, Dan Pennington, Paul Pfeffer, Jane Osbourn
bioRxiv 2020.05.20.106294; doi: https://doi.org/10.1101/2020.05.20.106294
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Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures
Jacob D. Galson, Sebastian Schaetzle, Rachael J. M. Bashford-Rogers, Matthew I. J. Raybould, Aleksandr Kovaltsuk, Gavin J. Kilpatrick, Ralph Minter, Donna K. Finch, Jorge Dias, Louisa James, Gavin Thomas, Wing-Yiu Jason Lee, Jason Betley, Olivia Cavlan, Alex Leech, Charlotte M. Deane, Joan Seoane, Carlos Caldas, Dan Pennington, Paul Pfeffer, Jane Osbourn
bioRxiv 2020.05.20.106294; doi: https://doi.org/10.1101/2020.05.20.106294

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