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TitleChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface.
Journal, issue, pagesiScience, Vol. 26, Issue 10, Page 107882, Year 2023
Publish dateOct 20, 2023
AuthorsTao Ni / Luiza Mendonça / Yanan Zhu / Andrew Howe / Julika Radecke / Pranav M Shah / Yuewen Sheng / Anna-Sophia Krebs / Helen M E Duyvesteyn / Elizabeth Allen / Teresa Lambe / Cameron Bisset / Alexandra Spencer / Susan Morris / David I Stuart / Sarah Gilbert / Peijun Zhang /
PubMed AbstractVaccines 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 ...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 . 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 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.
External linksiScience / PubMed:37766989 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution9.0 - 11.9 Å
Structure data

EMDB-16403: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C3 symmetry
Method: EM (subtomogram averaging) / Resolution: 9.0 Å

EMDB-16404: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C1 symmetry
Method: EM (subtomogram averaging) / Resolution: 9.7 Å

EMDB-16405: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E) in C3 symmetry
Method: EM (subtomogram averaging) / Resolution: 9.6 Å

EMDB-16406: Subtomogram averaging of a coronavirus spike in situ (ChAdOx1 19E) in C1 symmetry
Method: EM (subtomogram averaging) / Resolution: 11.9 Å

EMDB-16697: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C1 symmetry after 3D classification
Method: EM (subtomogram averaging) / Resolution: 10.6 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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