Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Piyada Supasa; Daming Zhou; Wanwisa Dejnirattisai; Chang Liu; Alexander J Mentzer; Helen M Ginn; Yuguang Zhao; Helen M E Duyvesteyn; Rungtiwa Nutalai; Aekkachai Tuekprakhon; Beibei Wang; Guido C Paesen; Jose Slon-Campos; César López-Camacho; Bassam Hallis; Naomi Coombes; Kevin R Bewley; Sue Charlton; Thomas S Walter; Eleanor Barnes; Susanna J Dunachie; Donal Skelly; Sheila F Lumley; Natalie Baker; Imam Shaik; Holly E Humphries; Kerry Godwin; Nick Gent; Alex Sienkiewicz; Christina Dold; Robert Levin; Tao Dong; Andrew J Pollard; Julian C Knight; Paul Klenerman; Derrick Crook; Teresa Lambe; Elizabeth Clutterbuck; Sagida Bibi; Amy Flaxman; Mustapha Bittaye; Sandra Belij-Rammerstorfer; Sarah Gilbert; David R Hall; Mark A Williams; Neil G Paterson; William James; Miles W Carroll; Elizabeth E Fry; Juthathip Mongkolsapaya; Jingshan Ren; David I Stuart; Gavin R Screaton

doi:10.1016/j.cell.2021.02.033

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Cell. 2021 Apr 15;184(8):2201-2211.e7. doi: 10.1016/j.cell.2021.02.033. Epub 2021 Feb 18.

Authors

Piyada Supasa¹, Daming Zhou², Wanwisa Dejnirattisai¹, Chang Liu³, Alexander J Mentzer⁴, Helen M Ginn⁵, Yuguang Zhao², Helen M E Duyvesteyn², Rungtiwa Nutalai¹, Aekkachai Tuekprakhon¹, Beibei Wang¹, Guido C Paesen², Jose Slon-Campos¹, César López-Camacho¹, Bassam Hallis⁶, Naomi Coombes⁶, Kevin R Bewley⁶, Sue Charlton⁶, Thomas S Walter², Eleanor Barnes⁷, Susanna J Dunachie⁸, Donal Skelly⁹, Sheila F Lumley¹⁰, Natalie Baker⁶, Imam Shaik⁶, Holly E Humphries⁶, Kerry Godwin⁶, Nick Gent⁶, Alex Sienkiewicz⁶, Christina Dold¹¹, Robert Levin¹², Tao Dong¹³, Andrew J Pollard¹¹, Julian C Knight¹⁴, Paul Klenerman⁷, Derrick Crook¹⁵, Teresa Lambe¹⁶, Elizabeth Clutterbuck¹¹, Sagida Bibi¹¹, Amy Flaxman¹⁶, Mustapha Bittaye¹⁶, Sandra Belij-Rammerstorfer¹⁶, Sarah Gilbert¹⁶, David R Hall⁵, Mark A Williams⁵, Neil G Paterson⁵, William James¹⁷, Miles W Carroll¹⁸, Elizabeth E Fry², Juthathip Mongkolsapaya¹⁹, Jingshan Ren²⁰, David I Stuart²¹, Gavin R Screaton²²

Affiliations

¹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
² Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
³ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
⁴ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵ Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
⁶ National Infection Service, Public Health England (PHE), Porton Down, Salisbury, UK.
⁷ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁸ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Centre For Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
⁹ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁰ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹¹ NIHR Oxford Biomedical Research Centre, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹² Worthing Hospital, Worthing, UK.
¹³ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
¹⁴ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁵ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁶ Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁷ Sir William Dunn School of Pathology University of Oxford, Oxford, UK.
¹⁸ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, UK.
¹⁹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Dean Office for Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Electronic address: [email protected].
²⁰ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. Electronic address: [email protected].
²¹ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK; Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, UK. Electronic address: [email protected].
²² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Electronic address: [email protected].

Abstract

SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

Keywords: B.1.1.7; IGHV3-53; Kent; SARS-CoV-2; antibody; escape; neutralization; variant.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology*
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology*
Antibodies, Viral / blood
Antibodies, Viral / immunology*
CHO Cells
COVID-19 / epidemiology
COVID-19 / immunology*
Chlorocebus aethiops
Cricetulus
HEK293 Cells
Humans
Pandemics
Protein Binding
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / immunology*
Structure-Activity Relationship
Vero Cells

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding