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 NavecaValdinete 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 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

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)4220-4236.e13
Number of pages30
JournalCell
Volume184
Issue number16
Early online date17 Jun 2021
DOIs
Publication statusPublished - 5 Aug 2021

Bibliographical note

Funding Information: Declaration of interests G.R.S. is on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. A.J.P. is Chair of UK Department Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID19 committee and is a member of the WHO’s 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. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine (PCT/GB2012/000467). T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project during the conduct of the study.

This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (2018-I2M-2-002 to D.I.S. and G.R.S.). H.M.E.D. and J. Ren are supported by the Wellcome Trust (101122/Z/13/Z), Y.Z. by Cancer Research UK (C375/A17721), D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1), and N.T. by the MRC (MC_PC_19060 and MC_PC_20016) and the Wellcome Trust (GB-CHC-210183). D.I.S. and G.R.S. are Jenner Investigators. We are also grateful for a Fast Grant from Fast Grants, the Mercatus Center for supporting the isolation of human monoclonal antibodies to SARS-CoV-2, and Schmidt Futures for supporting this work. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (090532/Z/09/Z). F.G.N. is a CNPq fellow and is supported by FAPEAM (PCTI-EmergeSaude/AM call 005/2020 and Rede Genomica de Vigilancia em Saude - REGESAM), Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (403276/2020-9), and Inova Fiocruz/ Fundaçao Oswaldo Cruz (VPPCB-007-FIO-18-2-30 - Geraçao de conhecimento). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). Virus used for the neutralization assays was isolated by Julian Druce, Doherty Centre, Melbourne, Australia. Chanice Knight, Emily Chiplin, Ross Fothergill, and Liz Penn contributed to assays. We acknowledge Diamond Light Source for time on Beamline I03 under Proposal lb27009 for COVID-19 Rapid Access. Huge thanks go to the teams, especially at the Diamond Light Source and Department of Structural Biology, Oxford University, that have enabled work to continue during the pandemic. The computational aspects of this research were supported by the Wellcome Trust Core Award Grant 203141/Z/16/Z and the NIHR Oxford BRC. The Oxford Vaccine work was supported by UK Research and Innovation, the Coalition for Epidemic Preparedness Innovations, the National Institute for Health Research (NIHR), the NIHR Oxford Biomedical Research Centre, and Thames Valley and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T-cell Immunology for COVID-19 (OPTIC) clinical team for participant sample collection, the Oxford Immunology Network Covid-19 Response T cell Consortium for laboratory support, and Red Avenue Foundation for their support. We acknowledge the rapid sharing of Victoria, B.1.1.7 and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided by Wendy Barclay and Thushan De Silva from the UKRI funded genotype to phenotype consortium G2P-UK. We thank The Secretariat of National Surveillance, Ministry of Health Brazil for assistance with obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by NIHR (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS), WT109965MA and NIH (U19 I082360). D.S. is an NIHR Academic Clinical Fellow. The team at the University of Witwatersrand was supported by The Bill & Melinda Gates Foundation (INV-016202). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Health, England.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publishers Copyright: © 2021 The Authors. Published by Elsevier Inc.

Citation: Liu C, Ginn HM, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. 2021;184(16):4220-4236.e13.

DOI:10.1016/j.cell.2021.06.020

Keywords

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

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