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Antibody evasion by the Brazilian 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, Guido C. Paesen, 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, 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, View ORCID ProfileSarah 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, View ORCID ProfileDavid I. Stuart, Gavin R. Screaton
doi: https://doi.org/10.1101/2021.03.12.435194
Wanwisa Dejnirattisai
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Daming Zhou
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Piyada Supasa
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Chang Liu
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
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Alexander J. Mentzer
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
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Helen M. Ginn
5Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
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Yuguang Zhao
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Helen M.E. Duyvesteyn
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Aekkachai Tuekprakhon
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Rungtiwa Nutalai
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Beibei Wang
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Guido C. Paesen
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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César López-Camacho
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Jose Slon-Campos
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Thomas S. Walter
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Donal Skelly
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
6Peter Medawar Building for Pathogen Research, Oxford, UK.
7Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Sue Ann Costa Clemens
8Institute of Global Health, University of Siena, Siena, Brazil; Department of Paediatrics, University of Oxford, Oxford, UK.
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Felipe Gomes Naveca
9Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.
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Valdinete Nascimento
9Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.
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Fernanda Nascimento
9Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.
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Cristiano Fernandes da Costa
10Fundação de Vigilância em Saúde do Amazonas, Manaus, Amazonas, Brazil
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Christina Dold
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
12Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
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Robert Levin
13Worthing Hospital, Worthing, UK.
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Tao Dong
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
14MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
15Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Andrew J. Pollard
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
12Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
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Julian C. Knight
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
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Derrick Crook
15Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Teresa Lambe
16Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Elizabeth Clutterbuck
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
12Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
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Sagida Bibi
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
12Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
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Amy Flaxman
16Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Mustapha Bittaye
16Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Sandra Belij-Rammerstorfer
16Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Sarah Gilbert
16Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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  • ORCID record for Sarah Gilbert
Miles W. Carroll
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
17National Infection Service, Public Health England (PHE), Porton Down, Salisbury, UK..
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Paul Klenerman
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
6Peter Medawar Building for Pathogen Research, Oxford, UK.
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
18Translational Gastroenterology Unit, University of Oxford, Oxford, UK
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Eleanor Barnes
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
6Peter Medawar Building for Pathogen Research, Oxford, UK.
11NIHR Oxford Biomedical Research Centre, Oxford, UK.
18Translational Gastroenterology Unit, University of Oxford, Oxford, UK
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Susanna J. Dunachie
4Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
6Peter Medawar Building for Pathogen Research, Oxford, UK.
19Centre For Tropical Medicine and Global Health, Nuffield Deptment of Medicine, University of Oxford, Oxford, UK.
20Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand. Department of Medicine, University of Oxford, Oxford, UK.
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Neil G. Paterson
5Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
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Mark A. Williams
5Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
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David R. Hall
5Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
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Ruben J. G. Hulswit
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Thomas A. Bowden
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Elizabeth E. Fry
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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Juthathip Mongkolsapaya
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
21Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Dean Office for Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
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  • For correspondence: dave@strubi.ox.ac.uk
Jingshan Ren
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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  • For correspondence: dave@strubi.ox.ac.uk
David I. Stuart
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
2Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
5Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
22Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, UK.
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  • For correspondence: dave@strubi.ox.ac.uk
Gavin R. Screaton
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
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  • For correspondence: dave@strubi.ox.ac.uk
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Summary

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: 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 RBD impact neutralisation. Monoclonal antibody 222 neutralises 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.

Competing Interest Statement

GRS sits on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. AJP is Chair of UK Dept. Health and Social Care (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID19 committee, and is a member of the WHO SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. The University of Oxford has protected intellectual property disclosed in this publication.

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 4.0 International license.
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Antibody evasion by the Brazilian 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, Guido C. Paesen, 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, 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, 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
bioRxiv 2021.03.12.435194; doi: https://doi.org/10.1101/2021.03.12.435194
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Antibody evasion by the Brazilian 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, Guido C. Paesen, 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, 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, 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
bioRxiv 2021.03.12.435194; doi: https://doi.org/10.1101/2021.03.12.435194

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