tetano
Editor, Senior Moderator
iScience
. 2023 Sep 12;26(10):107882.
doi: 10.1016/j.isci.2023.107882. eCollection 2023 Oct 20. ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
Tao Ni[SUP] 1 [/SUP], Luiza Mendonça[SUP] 1 [/SUP], Yanan Zhu[SUP] 1 [/SUP], Andrew Howe[SUP] 2 [/SUP], Julika Radecke[SUP] 2 [/SUP], Pranav M Shah[SUP] 1 3 [/SUP], Yuewen Sheng[SUP] 2 [/SUP], Anna-Sophia Krebs[SUP] 1 [/SUP], Helen M E Duyvesteyn[SUP] 1 [/SUP], Elizabeth Allen[SUP] 4 [/SUP], Teresa Lambe[SUP] 4 5 [/SUP], Cameron Bisset[SUP] 4 [/SUP], Alexandra Spencer[SUP] 4 [/SUP], Susan Morris[SUP] 6 [/SUP], David I Stuart[SUP] 1 2 3 6 [/SUP], Sarah Gilbert[SUP] 4 5 6 [/SUP], Peijun Zhang[SUP] 1 2 3 [/SUP]
Affiliations
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.
Keywords: Cell biology; Virology.
. 2023 Sep 12;26(10):107882.
doi: 10.1016/j.isci.2023.107882. eCollection 2023 Oct 20. ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
Tao Ni[SUP] 1 [/SUP], Luiza Mendonça[SUP] 1 [/SUP], Yanan Zhu[SUP] 1 [/SUP], Andrew Howe[SUP] 2 [/SUP], Julika Radecke[SUP] 2 [/SUP], Pranav M Shah[SUP] 1 3 [/SUP], Yuewen Sheng[SUP] 2 [/SUP], Anna-Sophia Krebs[SUP] 1 [/SUP], Helen M E Duyvesteyn[SUP] 1 [/SUP], Elizabeth Allen[SUP] 4 [/SUP], Teresa Lambe[SUP] 4 5 [/SUP], Cameron Bisset[SUP] 4 [/SUP], Alexandra Spencer[SUP] 4 [/SUP], Susan Morris[SUP] 6 [/SUP], David I Stuart[SUP] 1 2 3 6 [/SUP], Sarah Gilbert[SUP] 4 5 6 [/SUP], Peijun Zhang[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 37766989
- PMCID: PMC10520439
- DOI: 10.1016/j.isci.2023.107882
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.
Keywords: Cell biology; Virology.