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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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Publisher copy:
10.1016/j.isci.2023.107882

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author


More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
093305/Z/10/Z
203141/Z/16/Z
206422/Z/17/Z
060208/Z/00/Z
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/V001329/1
MR/N00065X/1
MC_PC_17137
More from this funder
Funder identifier:
https://ror.org/0472cxd90
Grant:
101021133
More from this funder
Funder identifier:
https://ror.org/02drdmm93
Grant:
2018-I2M-2-002


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:

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