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The impact of Spike mutations on SARS-CoV-2 neutralization

C Rees-Spear, L Muir, SA Griffith, J Heaney, Y Aldon, JL Snitselaar, P Thomas, C Graham, J Seow, N Lee, A Rosa, C Roustan, CF Houlihan, RW Sanders, View ORCID ProfileR Gupta, P Cherepanov, H Stauss, E Nastouli, KJ Doores, MJ van Gils, View ORCID ProfileLE McCoy on behalf of the SAFER Investigators
doi: https://doi.org/10.1101/2021.01.15.426849
C Rees-Spear
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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L Muir
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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SA Griffith
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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J Heaney
2Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK
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Y Aldon
3Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Netherlands
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JL Snitselaar
3Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Netherlands
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P Thomas
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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C Graham
4School of Immunology & Microbial Sciences, King’s College London, UK
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J Seow
4School of Immunology & Microbial Sciences, King’s College London, UK
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N Lee
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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A Rosa
5The Francis Crick Institute, UK
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C Roustan
5The Francis Crick Institute, UK
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CF Houlihan
2Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK
6Research Department of Infection, Division of Infection and Immunity, University College London
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RW Sanders
3Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Netherlands
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R Gupta
8Great Ormond Street Institute for Child Health, Infection, Immunity and Inflammation, University College London
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  • ORCID record for R Gupta
P Cherepanov
5The Francis Crick Institute, UK
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H Stauss
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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E Nastouli
2Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK
5The Francis Crick Institute, UK
8Great Ormond Street Institute for Child Health, Infection, Immunity and Inflammation, University College London
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KJ Doores
4School of Immunology & Microbial Sciences, King’s College London, UK
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MJ van Gils
3Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Netherlands
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LE McCoy
1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
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  • ORCID record for LE McCoy
  • For correspondence: L.mccoy@ucl.ac.uk
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Abstract

Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵¶ SAFER Investigators are listed in the supplementary information

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-ND 4.0 International license.
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Posted January 19, 2021.
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The impact of Spike mutations on SARS-CoV-2 neutralization
C Rees-Spear, L Muir, SA Griffith, J Heaney, Y Aldon, JL Snitselaar, P Thomas, C Graham, J Seow, N Lee, A Rosa, C Roustan, CF Houlihan, RW Sanders, R Gupta, P Cherepanov, H Stauss, E Nastouli, KJ Doores, MJ van Gils, LE McCoy
bioRxiv 2021.01.15.426849; doi: https://doi.org/10.1101/2021.01.15.426849
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The impact of Spike mutations on SARS-CoV-2 neutralization
C Rees-Spear, L Muir, SA Griffith, J Heaney, Y Aldon, JL Snitselaar, P Thomas, C Graham, J Seow, N Lee, A Rosa, C Roustan, CF Houlihan, RW Sanders, R Gupta, P Cherepanov, H Stauss, E Nastouli, KJ Doores, MJ van Gils, LE McCoy
bioRxiv 2021.01.15.426849; doi: https://doi.org/10.1101/2021.01.15.426849

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