The effect of spike mutations on SARS-CoV-2 neutralization
Chloe Rees-Spear,
Luke Muir,
Sarah A. Griffith,
Judith Heaney,
Yoann Aldon,
Jonne L. Snitselaar,
Peter Thomas,
Carl Graham,
Jeffrey Seow,
Nayung Lee,
Annachiara Rosa,
Chloe Roustan,
Catherine F. Houlihan,
Rogier W. Sanders,
Ravindra K. Gupta,
Peter Cherepanov,
Hans J. Stauss,
Eleni Nastouli,
Katie J. Doores,
Marit J. van Gils,
Laura E. McCoy
Affiliations
Chloe Rees-Spear
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Luke Muir
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Sarah A. Griffith
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Judith Heaney
Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK
Yoann Aldon
Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Jonne L. Snitselaar
Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Peter Thomas
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Carl Graham
School of Immunology and Microbial Sciences, King’s College London, London SE1 9RT, UK
Jeffrey Seow
School of Immunology and Microbial Sciences, King’s College London, London SE1 9RT, UK
Nayung Lee
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Annachiara Rosa
The Francis Crick Institute, London NW1 1AT, UK
Chloe Roustan
The Francis Crick Institute, London NW1 1AT, UK
Catherine F. Houlihan
Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK; Research Department of Infection, Division of Infection and Immunity, University College London, London WC1 6BT, UK
Rogier W. Sanders
Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Ravindra K. Gupta
Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Peter Cherepanov
The Francis Crick Institute, London NW1 1AT, UK
Hans J. Stauss
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK
Eleni Nastouli
Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK; The Francis Crick Institute, London NW1 1AT, UK; Great Ormond Street Institute for Child Health, Infection, Immunity and Inflammation, University College London, London WC1N 1EH, UK
Katie J. Doores
School of Immunology and Microbial Sciences, King’s College London, London SE1 9RT, UK
Marit J. van Gils
Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Laura E. McCoy
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK; Corresponding author
Summary: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.
