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ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface

DOI: 10.1016/j.isci.2023.107882 DOI Help

Authors: Tao Ni (University of Oxford) , Luiza Mendonca (University of Oxford) , Yanan Zhu (University of Oxford) , Andrew Howe (Diamond Light Source) , Julika Radecke (Diamond Light Source) , Pranav M. Shah (University of Oxford; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford) , Yuewen Sheng (Diamond Light Source) , Anna-Sophia Krebs (University of Oxford) , Helen M. E. Duyvesteyn (University of Oxford) , Elizabeth Allen (University of Oxford) , Teresa Lambe (University of Oxford; NIHR Oxford Biomedical Research Centre) , Cameron Bisset (University of Oxford) , Alexandra Spencer (University of Oxford) , Susan Morris (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford) , Sarah Gilbert (University of Oxford; NIHR Oxford Biomedical Research Centre) , Peijun Zhang (University of Oxford; Diamond Light Source; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Iscience

State: Published (Approved)
Published: September 2023
Diamond Proposal Number(s): 26987

Open Access Open Access

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.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond , Krios III-Titan Krios III at Diamond , Krios IV-Titan Krios IV at Diamond

Added On: 13/09/2023 08:05

Documents:
1-s2.0-S2589004223019594-main.pdf

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Imaging Tomography Cryo Electron Tomography (Cryo ET)