Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

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

doi:10.1016/j.cell.2021.02.037

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Cell. 2021 Apr 29;184(9):2348-2361.e6. doi: 10.1016/j.cell.2021.02.037. Epub 2021 Feb 23.

Authors

Daming Zhou¹, Wanwisa Dejnirattisai², Piyada Supasa², Chang Liu³, Alexander J Mentzer⁴, Helen M Ginn⁵, Yuguang Zhao¹, Helen M E Duyvesteyn¹, Aekkachai Tuekprakhon², Rungtiwa Nutalai², Beibei Wang², Guido C Paesen¹, Cesar Lopez-Camacho², Jose Slon-Campos², Bassam Hallis⁶, Naomi Coombes⁶, Kevin Bewley⁶, Sue Charlton⁶, Thomas S Walter², Donal Skelly⁷, Sheila F Lumley⁸, Christina Dold⁹, Robert Levin¹⁰, Tao Dong¹¹, Andrew J Pollard⁹, Julian C Knight¹², Derrick Crook¹³, Teresa Lambe¹⁴, Elizabeth Clutterbuck⁹, Sagida Bibi⁹, Amy Flaxman¹⁴, Mustapha Bittaye¹⁴, Sandra Belij-Rammerstorfer¹⁴, Sarah Gilbert¹⁴, William James¹⁵, Miles W Carroll¹⁶, Paul Klenerman¹⁷, Eleanor Barnes¹⁷, Susanna J Dunachie¹⁸, Elizabeth E Fry¹, Juthathip Mongkolsapaya¹⁹, Jingshan Ren²⁰, David I Stuart²¹, Gavin R Screaton²²

Affiliations

¹ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, 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 Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, 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; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁸ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹ NIHR Oxford Biomedical Research Centre, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁰ Worthing Hospital, Worthing, UK.
¹¹ 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.
¹² 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; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹³ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁴ Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁵ Sir William Dunn School of Pathology University of Oxford, Oxford, UK.
¹⁶ 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.
¹⁷ 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.
¹⁸ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Medicine, University of Oxford, 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.
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: jmongkol@well.ox.ac.uk.
²⁰ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. Electronic address: ren@strubi.ox.ac.uk.
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: dave.stuart@diamond.ac.uk.
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: gavin.screaton@medsci.ox.ac.uk.

Abstract

The race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.

Keywords: ACE2; B.1.351; SARS-CoV-2; South Africa; antibody; escape; neutralization; receptor-binding domain; vaccine; variant.

Publication types

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

MeSH terms

Animals
Antibodies, Monoclonal / immunology
COVID-19 / immunology
COVID-19 / therapy
COVID-19 / virology
COVID-19 Serotherapy
COVID-19 Vaccines / blood*
COVID-19 Vaccines / immunology*
Chlorocebus aethiops
Clinical Trials as Topic
HEK293 Cells
Humans
Immunization, Passive
Models, Molecular
Mutation / genetics
Neutralization Tests
Protein Binding
SARS-CoV-2 / chemistry
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
Vero Cells

Substances

Antibodies, Monoclonal
COVID-19 Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding