Journal article

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2

Daniel Watterson, Danushka K Wijesundara, Naphak Modhiran, Francesca L Mordant, Zheyi Li, Michael S Avumegah, Christopher Ld McMillan, Julia Lackenby, Kate Guilfoyle, Geert van Amerongen, Koert Stittelaar, Stacey TM Cheung, Summa Bibby, Mallory Daleris, Kym Hoger, Marianne Gillard, Eve Radunz, Martina L Jones, Karen Hughes, Ben Hughes Show all

CLINICAL & TRANSLATIONAL IMMUNOLOGY | WILEY | Published : 2021

Abstract

Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia). Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology stud..

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Grants

Awarded by NHMRC


Funding Acknowledgements

This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo-EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS-CoV-2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic & Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes-Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis.