ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
© 2023 The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 10 vom: 20. Okt., Seite 107882 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ni, Tao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 20.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.107882 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Virology | |
| 700 | 1 | |a Mendonça, Luiza |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Howe, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Radecke, Julika |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Pranav M |e verfasserin |4 aut | |
| 700 | 1 | |a Sheng, Yuewen |e verfasserin |4 aut | |
| 700 | 1 | |a Krebs, Anna-Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Duyvesteyn, Helen M E |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Lambe, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Bisset, Cameron |e verfasserin |4 aut | |
| 700 | 1 | |a Spencer, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Stuart, David I |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Peijun |e verfasserin |4 aut | |
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