Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Chang Liu; Helen M Ginn; Wanwisa Dejnirattisai; Piyada Supasa; Beibei Wang; Aekkachai Tuekprakhon; Rungtiwa Nutalai; Daming Zhou; Alexander J Mentzer; Yuguang Zhao; Helen M E Duyvesteyn; César López-Camacho; Jose Slon-Campos; Thomas S Walter; Donal Skelly; Sile Ann Johnson; Thomas G Ritter; Chris Mason; 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; Nigel Temperton; 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; Tariq Malik; Miles W Carroll; Paul Klenerman; Eleanor Barnes; Susanna J Dunachie; Vicky Baillie; Natali Serafin; Zanele Ditse; Kelly Da Silva; Neil G Paterson; Mark A Williams; David R Hall; Shabir Madhi; Marta C Nunes; Philip Goulder; Elizabeth E Fry; Juthathip Mongkolsapaya; Jingshan Ren; David I Stuart; Gavin R Screaton

doi:10.1016/j.cell.2021.06.020

Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Cell. 2021 Aug 5;184(16):4220-4236.e13. doi: 10.1016/j.cell.2021.06.020. Epub 2021 Jun 17.

Authors

Chang Liu¹, Helen M Ginn², Wanwisa Dejnirattisai³, Piyada Supasa³, Beibei Wang³, Aekkachai Tuekprakhon³, Rungtiwa Nutalai³, Daming Zhou⁴, Alexander J Mentzer⁵, Yuguang Zhao⁴, Helen M E Duyvesteyn⁴, César López-Camacho³, Jose Slon-Campos³, Thomas S Walter⁴, Donal Skelly⁶, Sile Ann Johnson⁷, Thomas G Ritter⁸, Chris Mason⁸, Sue Ann Costa Clemens⁹, Felipe Gomes Naveca¹⁰, Valdinete Nascimento¹⁰, Fernanda Nascimento¹⁰, Cristiano Fernandes da Costa¹¹, Paola Cristina Resende¹², Alex Pauvolid-Correa¹³, Marilda M Siqueira¹², Christina Dold¹⁴, Nigel Temperton¹⁵, Tao Dong¹⁶, Andrew J Pollard¹⁴, Julian C Knight¹⁷, Derrick Crook¹⁸, Teresa Lambe¹⁹, Elizabeth Clutterbuck¹⁴, Sagida Bibi¹⁴, Amy Flaxman¹⁹, Mustapha Bittaye¹⁹, Sandra Belij-Rammerstorfer¹⁹, Sarah C Gilbert¹⁹, Tariq Malik²⁰, Miles W Carroll²¹, Paul Klenerman²², Eleanor Barnes²², Susanna J Dunachie²³, Vicky Baillie²⁴, Natali Serafin²⁴, Zanele Ditse²⁴, Kelly Da Silva²⁴, Neil G Paterson², Mark A Williams², David R Hall², Shabir Madhi²⁴, Marta C Nunes²⁴, Philip Goulder²⁵, Elizabeth E Fry⁴, Juthathip Mongkolsapaya²⁶, Jingshan Ren²⁷, David I Stuart²⁸, Gavin R Screaton²⁹

Affiliations

¹ 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.
² Diamond Light Source Ltd., Harwell Science & Innovation Campus, Didcot, UK.
³ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁴ Division of Structural Biology, The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, 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 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.
⁷ Peter Medawar Building for Pathogen Research, Oxford, UK.
⁸ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁹ Institute of Global Health, University of Siena, Siena, Brazil; Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁰ Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.
¹¹ Fundação de Vigilância em Saúde do Amazonas, Manaus, Amazonas, Brazil.
¹² Laboratorio de vírus respiratórios-IOC/FIOCRUZ, Rio de Janeiro, Brazil.
¹³ Laboratorio de vírus respiratórios-IOC/FIOCRUZ, Rio de Janeiro, Brazil; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
¹⁴ NIHR Oxford Biomedical Research Centre, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁵ Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich, Chatham Maritime, Kent ME4 4TB, UK.
¹⁶ 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.
¹⁷ 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.
¹⁸ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁹ Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
²⁰ National Infection Service, Public Health England (PHE), Porton Down, Salisbury, UK.
²¹ 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.
²² 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.
²³ 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.
²⁴ South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²⁵ Peter Medawar Building for Pathogen Research, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
²⁶ 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.
²⁷ Division of Structural Biology, The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: ren@strubi.ox.ac.uk.
²⁸ 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; Diamond Light Source Ltd., Harwell Science & Innovation Campus, Didcot, UK; Division of Structural Biology, The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, UK. Electronic address: dave@strubi.ox.ac.uk.
²⁹ 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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the United Kingdom. Here we study the ability of monoclonal antibodies and convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2, complement this with structural analyses of Fab/receptor binding domain (RBD) complexes, and map the antigenic space of current variants. Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2, suggesting that individuals infected previously by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insights for immunization policy with future variant vaccines in non-immune populations.

Keywords: B.1.617; Delta variant; Receptor-binding-domain; SARS-CoV-2; antibody; escape; neutralization; structure; vaccine; variant.

Publication types

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

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology*
Antigen-Antibody Complex / chemistry
COVID-19 / pathology
COVID-19 / therapy
COVID-19 / virology
COVID-19 Serotherapy
COVID-19 Vaccines / administration & dosage
COVID-19 Vaccines / immunology*
Chlorocebus aethiops
Crystallography, X-Ray
Humans
Immunization, Passive
Neutralization Tests
Protein Domains / immunology
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
SARS-CoV-2 / isolation & purification
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / immunology
Vero Cells

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Antigen-Antibody Complex
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding