ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface

Tao Ni; Luiza Mendonça; Yanan Zhu; Andrew Howe; Julika Radecke; Pranav M. Shah; Yuewen Sheng; Anna-Sophia Krebs; Helen M.E. Duyvesteyn; Elizabeth Allen; Teresa Lambe; Cameron Bisset; Alexandra Spencer; Susan Morris; David I. Stuart; Sarah Gilbert; Peijun Zhang

iScience (Oct 2023)

ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface

Tao Ni,
Luiza Mendonça,
Yanan Zhu,
Andrew Howe,
Julika Radecke,
Pranav M. Shah,
Yuewen Sheng,
Anna-Sophia Krebs,
Helen M.E. Duyvesteyn,
Elizabeth Allen,
Teresa Lambe,
Cameron Bisset,
Alexandra Spencer,
Susan Morris,
David I. Stuart,
Sarah Gilbert,
Peijun Zhang

Affiliations

Tao Ni: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Luiza Mendonça: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Yanan Zhu: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Andrew Howe: Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Julika Radecke: Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Pranav M. Shah: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK
Yuewen Sheng: Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Anna-Sophia Krebs: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Helen M.E. Duyvesteyn: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Elizabeth Allen: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Teresa Lambe: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UK
Cameron Bisset: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Alexandra Spencer: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Susan Morris: Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
David I. Stuart: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK; Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
Sarah Gilbert: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UK; Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
Peijun Zhang: Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK; Corresponding author

Journal volume & issue: Vol. 26, no. 10
p. 107882

Abstract

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Summary: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven to be an effective means of decreasing COVID-19 mortality, hospitalization rates, and transmission. One of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Using cryo-electron tomography and subtomogram averaging, we determined the native structures of the vaccine product expressed on cell surfaces in situ. We show that ChAdOx1-vectored vaccines expressing the Beta SARS-CoV-2 variant produce abundant native prefusion spikes predominantly in one-RBD-up conformation. Furthermore, the ChAdOx1-vectored HexaPro-stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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