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

doi:10.1016/j.isci.2023.107882

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

iScience. 2023 Sep 12;26(10):107882. doi: 10.1016/j.isci.2023.107882. eCollection 2023 Oct 20.

Authors

Tao Ni¹, Luiza Mendonça¹, Yanan Zhu¹, Andrew Howe², Julika Radecke², Pranav M Shah^{1

3}, Yuewen Sheng², Anna-Sophia Krebs¹, Helen M E Duyvesteyn¹, Elizabeth Allen⁴, Teresa Lambe^{4

5}, Cameron Bisset⁴, Alexandra Spencer⁴, Susan Morris⁶, David I Stuart^{1

2

3

6}, Sarah Gilbert^{4

5

6}, Peijun Zhang^{1

2

3}

Affiliations

¹ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
² Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
³ Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.
⁴ The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
⁵ NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UK.
⁶ Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK.

Abstract

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.

Keywords: Cell biology; Virology.

Abstract

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