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 L.D. McMillan, Julia Lackenby, Kate Guilfoyle, Geert van Amerongen, Koert Stittelaar, Stacey T.M. Cheung, Summa Bibby, Mallory Daleris, Kym Hoger, Marianne Gillard, Eve Radunz, Martina L. Jones, Karen Hughes, Ben HughesJustin Goh, David Edwards, Judith Scoble, Lesley Pearce, Lukasz Kowalczyk, Tram Phan, Mylinh La, Louis Lu, Tam Pham, Qi Zhou, David A. Brockman, Sherry J. Morgan, Cora Lau, Mai H. Tran, Peter Tapley, Fernando Villalón-Letelier, James Barnes, Andrew Young, Noushin Jaberolansar, Connor A.P. Scott, Ariel Isaacs, Alberto A. Amarilla, Alexander A. Khromykh, Judith M.A. van den Brand, Patrick C. Reading, Charani Ranasinghe, Kanta Subbarao, Trent P. Munro, Paul R. Young*, Keith J. Chappell*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    42 Citations (Scopus)

    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 studies in rat. Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2–8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

    Original languageEnglish
    Article numbere1269
    JournalClinical and Translational Immunology
    Volume10
    Issue number4
    DOIs
    Publication statusPublished - 2021

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