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

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

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Article number	107882
Journal	iScience
Volume	26
Issue number	10
DOIs	https://doi.org/10.1016/j.isci.2023.107882
State	Published - Oct 20 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

Cell biology
Virology

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2023.107882

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Ni, T., Mendonça, L., Zhu, Y., Howe, A., Radecke, J., Shah, P. M., Sheng, Y., Krebs, A. S., Duyvesteyn, H. M. E., Allen, E., Lambe, T., Bisset, C., Spencer, A., Morris, S., Stuart, D. I., Gilbert, S., & Zhang, P. (2023). ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface. iScience, 26(10), Article 107882. https://doi.org/10.1016/j.isci.2023.107882

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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.",

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doi = "10.1016/j.isci.2023.107882",

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AU - Ni, Tao

AU - Mendonça, Luiza

AU - Zhu, Yanan

AU - Howe, Andrew

AU - Radecke, Julika

AU - Shah, Pranav M.

AU - Sheng, Yuewen

AU - Krebs, Anna Sophia

AU - Duyvesteyn, Helen M.E.

AU - Allen, Elizabeth

AU - Lambe, Teresa

AU - Bisset, Cameron

AU - Spencer, Alexandra

AU - Morris, Susan

AU - Stuart, David I.

AU - Gilbert, Sarah

AU - Zhang, Peijun

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N2 - 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.

AB - 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.

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KW - Virology

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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