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Title | ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface. |
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Journal, issue, pages | iScience, Vol. 26, Issue 10, Page 107882, Year 2023 |
Publish date | Oct 20, 2023 |
Authors | Tao 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 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 ...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 links | iScience / PubMed:37766989 / PubMed Central |
Methods | EM (subtomogram averaging) |
Resolution | 9.0 - 11.9 Å |
Structure data | EMDB-16403: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C3 symmetry EMDB-16404: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C1 symmetry EMDB-16405: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E) in C3 symmetry EMDB-16406: Subtomogram averaging of a coronavirus spike in situ (ChAdOx1 19E) in C1 symmetry EMDB-16697: Subtomogram averaging of a coronavirus spike (ChAdOx1 19E6) in C1 symmetry after 3D classification |
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