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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 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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Preprint server copy:
10.1101/2023.05.22.541685

Authors

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 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:
206422/Z/17/Z
203141/Z/16/Z
093305/Z/10/Z
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/N00065X/1
MR/V001329/1
More from this funder
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:
English
Pubs id:
1345346
Local pid:
pubs:1345346
Source identifiers:
W4377983361
Deposit date:
2026-05-29
ARK identifier:

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