ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
Abstract Vaccines against 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 surfacesin 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 demonstratein situstructure 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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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ni, Tao [VerfasserIn] |
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| doi: |
10.1101/2023.05.22.541685 |
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| PPN (Katalog-ID): |
XBI039678717 |
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| 520 | |a Abstract Vaccines against 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 surfacesin 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 demonstratein situstructure 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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| 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 |0 (orcid)0000-0002-5815-5537 |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 |0 (orcid)0000-0001-7958-6961 |4 aut | |
| 700 | 1 | |a Morris, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Stuart, David I. |e verfasserin |0 (orcid)0000-0002-3426-4210 |4 aut | |
| 700 | 1 | |a Gilbert, Sarah |e verfasserin |0 (orcid)0000-0002-6823-9750 |4 aut | |
| 700 | 1 | |a Zhang, Peijun |e verfasserin |0 (orcid)0000-0003-1803-691X |4 aut | |
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