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- Publisher Website: 10.1016/j.isci.2023.107882
- Scopus: eid_2-s2.0-85172000766
- WOS: WOS:001123033600001
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Article: ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
Title | ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface |
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Authors | |
Keywords | Cell biology Virology |
Issue Date | 11-Sep-2023 |
Publisher | Cell Press |
Citation | iScience, 2023, v. 26, n. 10 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/338089 |
ISSN | 2023 Impact Factor: 4.6 2023 SCImago Journal Rankings: 1.497 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ni, Tao | - |
dc.contributor.author | Mendonça, Luiza | - |
dc.contributor.author | Zhu, Yanan | - |
dc.contributor.author | Howe, Andrew | - |
dc.contributor.author | Radecke, Julika | - |
dc.contributor.author | Shah, Pranav M | - |
dc.contributor.author | Sheng, Yuewen | - |
dc.contributor.author | Krebs, Anna-Sophia | - |
dc.contributor.author | Duyvesteyn, Helen ME | - |
dc.contributor.author | Allen, Elizabeth | - |
dc.contributor.author | Lambe, Teresa | - |
dc.contributor.author | Bisset, Cameron | - |
dc.contributor.author | Spencer, Alexandra | - |
dc.contributor.author | Morris, Susan | - |
dc.contributor.author | Stuart, David I | - |
dc.contributor.author | Gilbert, Sarah | - |
dc.contributor.author | Zhang, Peijun | - |
dc.date.accessioned | 2024-03-11T10:26:10Z | - |
dc.date.available | 2024-03-11T10:26:10Z | - |
dc.date.issued | 2023-09-11 | - |
dc.identifier.citation | iScience, 2023, v. 26, n. 10 | - |
dc.identifier.issn | 2589-0042 | - |
dc.identifier.uri | http://hdl.handle.net/10722/338089 | - |
dc.description.abstract | <p>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 <em>in situ</em>. 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 <em>in situ</em> 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. <br></p> | - |
dc.language | eng | - |
dc.publisher | Cell Press | - |
dc.relation.ispartof | iScience | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Cell biology | - |
dc.subject | Virology | - |
dc.title | ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.isci.2023.107882 | - |
dc.identifier.scopus | eid_2-s2.0-85172000766 | - |
dc.identifier.volume | 26 | - |
dc.identifier.issue | 10 | - |
dc.identifier.eissn | 2589-0042 | - |
dc.identifier.isi | WOS:001123033600001 | - |
dc.identifier.issnl | 2589-0042 | - |