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Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine

View ORCID ProfileYasunori Watanabe, Luiza Mendonça, View ORCID ProfileElizabeth R. Allen, Andrew Howe, Mercede Lee, View ORCID ProfileJoel D. Allen, Himanshi Chawla, David Pulido, Francesca Donnellan, Hannah Davies, Marta Ulaszewska, Sandra Belij-Rammerstorfer, Susan Morris, Anna-Sophia Krebs, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Piyada Supasa, Gavin R. Screaton, Catherine M. Green, Teresa Lambe, Peijun Zhang, View ORCID ProfileSarah C. Gilbert, View ORCID ProfileMax Crispin
doi: https://doi.org/10.1101/2021.01.15.426463
Yasunori Watanabe
1School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK
2Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
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Luiza Mendonça
3Division of Structural Biology, University of Oxford, Wellcome Centre for Human Genetics, Oxford, OX3 7BN, UK
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Elizabeth R. Allen
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Andrew Howe
5Electron Bio-imaging Centre, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK
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Mercede Lee
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Joel D. Allen
1School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK
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Himanshi Chawla
1School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK
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David Pulido
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Francesca Donnellan
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Hannah Davies
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Marta Ulaszewska
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Sandra Belij-Rammerstorfer
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
6NIHR Oxford Biomedical Research Centre, Oxford, UK
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Susan Morris
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Anna-Sophia Krebs
3Division of Structural Biology, University of Oxford, Wellcome Centre for Human Genetics, Oxford, OX3 7BN, UK
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Wanwisa Dejnirattisai
7The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
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Juthathip Mongkolsapaya
7The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
9Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
10Chinese Academy of Medical Science(CAMS) Oxford Institute (COI), University of Oxford, Oxford, U.K.
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Piyada Supasa
7The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
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Gavin R. Screaton
7The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
8Division of Medical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
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Catherine M. Green
7The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
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Teresa Lambe
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
6NIHR Oxford Biomedical Research Centre, Oxford, UK
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  • For correspondence: max.crispin@soton.ac.uk peijun@strubi.ox.ac.uk sarah.gilbert@ndm.ox.ac.uk teresa.lambe@ndm.ox.ac.uk
Peijun Zhang
3Division of Structural Biology, University of Oxford, Wellcome Centre for Human Genetics, Oxford, OX3 7BN, UK
5Electron Bio-imaging Centre, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK
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  • For correspondence: max.crispin@soton.ac.uk peijun@strubi.ox.ac.uk sarah.gilbert@ndm.ox.ac.uk teresa.lambe@ndm.ox.ac.uk
Sarah C. Gilbert
4The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
6NIHR Oxford Biomedical Research Centre, Oxford, UK
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  • For correspondence: max.crispin@soton.ac.uk peijun@strubi.ox.ac.uk sarah.gilbert@ndm.ox.ac.uk teresa.lambe@ndm.ox.ac.uk
Max Crispin
1School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK
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  • ORCID record for Max Crispin
  • For correspondence: max.crispin@soton.ac.uk peijun@strubi.ox.ac.uk sarah.gilbert@ndm.ox.ac.uk teresa.lambe@ndm.ox.ac.uk
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Abstract

Vaccine development against the SARS-CoV-2 virus focuses on the principal target of the neutralizing immune response, the spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for the delivery of viral antigen, but it is important for the generation of neutralizing antibodies that they produce appropriately processed and assembled viral antigen that mimics that observed on the SARS-CoV-2 virus. Here, we describe the structure, conformation and glycosylation of the S protein derived from the adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate native-like post-translational processing and assembly, and reveal the expression of S proteins on the surface of cells adopting the trimeric prefusion conformation. The data presented here confirms the use of ChAdOx1 adenovirus vectors as a leading platform technology for SARS-CoV-2 vaccines.

Competing Interest Statement

Oxford University has entered into a partnership with Astra Zeneca for further development of ChAdOx1 nCoV-19. SCG is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and consultant to Vaccitech.

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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Posted January 19, 2021.
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Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine
Yasunori Watanabe, Luiza Mendonça, Elizabeth R. Allen, Andrew Howe, Mercede Lee, Joel D. Allen, Himanshi Chawla, David Pulido, Francesca Donnellan, Hannah Davies, Marta Ulaszewska, Sandra Belij-Rammerstorfer, Susan Morris, Anna-Sophia Krebs, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Piyada Supasa, Gavin R. Screaton, Catherine M. Green, Teresa Lambe, Peijun Zhang, Sarah C. Gilbert, Max Crispin
bioRxiv 2021.01.15.426463; doi: https://doi.org/10.1101/2021.01.15.426463
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Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine
Yasunori Watanabe, Luiza Mendonça, Elizabeth R. Allen, Andrew Howe, Mercede Lee, Joel D. Allen, Himanshi Chawla, David Pulido, Francesca Donnellan, Hannah Davies, Marta Ulaszewska, Sandra Belij-Rammerstorfer, Susan Morris, Anna-Sophia Krebs, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Piyada Supasa, Gavin R. Screaton, Catherine M. Green, Teresa Lambe, Peijun Zhang, Sarah C. Gilbert, Max Crispin
bioRxiv 2021.01.15.426463; doi: https://doi.org/10.1101/2021.01.15.426463

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