Journal article
ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.9MB, Terms of use)
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- Publisher copy:
- 10.1016/j.isci.2023.107882
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 093305/Z/10/Z
- 203141/Z/16/Z
- 206422/Z/17/Z
- 060208/Z/00/Z
+ Medical Research Council
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- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/V001329/1
- MR/N00065X/1
- MC_PC_17137
+ European Research Council
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- Funder identifier:
- https://ror.org/0472cxd90
- Grant:
- 101021133
+ Chinese Academy of Medical Sciences & Peking Union Medical College
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- Funder identifier:
- https://ror.org/02drdmm93
- Grant:
- 2018-I2M-2-002
+ Biotechnology and Biological Sciences Research Council
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- Funder identifier:
- https://ror.org/00cwqg982
- Publisher:
- Cell Press
- Journal:
- iScience More from this journal
- Volume:
- 26
- Issue:
- 10
- Article number:
- 107882
- Place of publication:
- United States
- Publication date:
- 2023-09-12
- Acceptance date:
- 2023-09-07
- DOI:
- EISSN:
-
2589-0042
- Pmid:
-
37766989
- Language:
-
English
- Pubs id:
-
1537298
- Local pid:
-
pubs:1537298
- Source identifiers:
-
W4386637635
- Deposit date:
-
2026-04-01
- ARK identifier:
Terms of use
- Copyright holder:
- Ni et al.
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Licence:
- CC Attribution (CC BY)
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