Antibody evasion by the P.1 strain of SARS-CoV-2

Wanwisa Dejnirattisai; Daming Zhou; Piyada Supasa; Chang Liu; Alexander J Mentzer; Helen M Ginn; Yuguang Zhao; Helen M E Duyvesteyn; Aekkachai Tuekprakhon; Rungtiwa Nutalai; Beibei Wang; César López-Camacho; Jose Slon-Campos; Thomas S Walter; Donal Skelly; Sue Ann Costa Clemens; Felipe Gomes Naveca; Valdinete Nascimento; Fernanda Nascimento; Cristiano Fernandes da Costa; Paola Cristina Resende; Alex Pauvolid-Correa; Marilda M Siqueira; 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 C Gilbert; Miles W Carroll; Paul Klenerman; Eleanor Barnes; Susanna J Dunachie; Neil G Paterson; Mark A Williams; David R Hall; Ruben J G Hulswit; Thomas A Bowden; Elizabeth E Fry; Juthathip Mongkolsapaya; Jingshan Ren; David I Stuart; Gavin R Screaton

doi:10.1016/j.cell.2021.03.055

Antibody evasion by the P.1 strain of SARS-CoV-2

Cell. 2021 May 27;184(11):2939-2954.e9. doi: 10.1016/j.cell.2021.03.055. Epub 2021 Mar 30.

Authors

Wanwisa Dejnirattisai¹, Daming Zhou², Piyada Supasa³, Chang Liu⁴, Alexander J Mentzer⁵, Helen M Ginn⁶, Yuguang Zhao², Helen M E Duyvesteyn², Aekkachai Tuekprakhon³, Rungtiwa Nutalai³, Beibei Wang³, César López-Camacho³, Jose Slon-Campos³, Thomas S Walter², Donal Skelly⁷, Sue Ann Costa Clemens⁸, Felipe Gomes Naveca⁹, Valdinete Nascimento⁹, Fernanda Nascimento⁹, Cristiano Fernandes da Costa¹⁰, Paola Cristina Resende¹¹, Alex Pauvolid-Correa¹², Marilda M Siqueira¹¹, Christina Dold¹³, Robert Levin¹⁴, Tao Dong¹⁵, Andrew J Pollard¹³, Julian C Knight¹⁶, Derrick Crook¹⁷, Teresa Lambe¹⁸, Elizabeth Clutterbuck¹³, Sagida Bibi¹³, Amy Flaxman¹⁸, Mustapha Bittaye¹⁸, Sandra Belij-Rammerstorfer¹⁸, Sarah C Gilbert¹⁸, Miles W Carroll¹⁹, Paul Klenerman²⁰, Eleanor Barnes²⁰, Susanna J Dunachie²¹, Neil G Paterson⁶, Mark A Williams⁶, David R Hall⁶, Ruben J G Hulswit², Thomas A Bowden², Elizabeth E Fry², Juthathip Mongkolsapaya²², Jingshan Ren²³, David I Stuart²⁴, Gavin R Screaton²⁵

Affiliations

¹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: dwanwisa@well.ox.ac.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.
⁴ 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.
⁵ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁶ Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, 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 Institute of Global Health, University of Siena, Siena, Brazil; Department of Paediatrics, University of Oxford, Oxford, UK.
⁹ Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, FIOCRUZ, Manaus, Amazonas, Brazil.
¹⁰ Fundação de Vigilância em Saúde do Amazonas, Manaus, Amazonas, Brazil.
¹¹ Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
¹² Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United States.
¹³ NIHR Oxford Biomedical Research Centre, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁴ Worthing Hospital, Worthing, UK.
¹⁵ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁶ 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; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁷ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁸ Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁹ 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.
²⁰ 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.
²¹ 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, Department of Medicine, University of Oxford, Oxford, 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; 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.
²³ 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.
²⁴ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 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@strubi.ox.ac.uk.
²⁵ 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

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Keywords: P.1; RBD; SARS-CoV-2; VH3-53; antibody; escape; neutralization; spike; structure; variant.

Publication types

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

MeSH terms

Antibodies, Monoclonal / immunology*
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
Binding Sites
COVID-19 / immunology*
COVID-19 / therapy
COVID-19 / virology
COVID-19 Serotherapy
Cell Line
Humans
Immune Evasion
Immunization, Passive
Mutation
Protein Binding
Protein Domains
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
Sequence Deletion
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*
Vaccination
Vaccines / immunology

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding