ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface
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
Affiliations
Tao Ni
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Luiza Mendonça
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Yanan Zhu
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Andrew Howe
Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Julika Radecke
Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Pranav M. Shah
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK
Yuewen Sheng
Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
Anna-Sophia Krebs
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Helen M.E. Duyvesteyn
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Elizabeth Allen
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Teresa Lambe
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UK
Cameron Bisset
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Alexandra Spencer
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
Susan Morris
Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
David I. Stuart
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK; Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
Sarah Gilbert
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UK; Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, OX3 7TY, UK
Peijun Zhang
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, UK; Corresponding author
Summary: 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.
