Preprint
ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
- Abstract:
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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 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.
- Publication status:
- Published
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- Files:
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(Preview, Pre-print, pdf, 2.5MB, Terms of use)
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- Preprint server copy:
- 10.1101/2023.05.22.541685
Authors
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 206422/Z/17/Z
- 203141/Z/16/Z
- 093305/Z/10/Z
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/N00065X/1
- MR/V001329/1
- Funder identifier:
- https://ror.org/0187kwz08
- Grant:
- COV19OxfordVaccine01
- Preprint server:
- bioRxiv
- Publication date:
- 2023-05-24
- Acceptance date:
- 2023-05-22
- DOI:
- Server owner:
- Cold Spring Harbor Laboratory
- Language:
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English
- Pubs id:
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1345346
- Local pid:
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pubs:1345346
- Source identifiers:
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W4377983361
- Deposit date:
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2026-05-29
- ARK identifier:
Terms of use
- Copyright holder:
- Ni et al.
- Copyright date:
- 2023
- Rights statement:
- The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
- Notes:
- This is a preprint of ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface.
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