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; Justin 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 Ap Scott; Ariel Isaacs; Alberto A Amarilla; Alexander A Khromykh; Judith Ma van den Brand; Patrick C Reading; Charani Ranasinghe; Kanta Subbarao; Trent P Munro; Paul R Young; Keith J Chappell

doi:10.1002/cti2.1269

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

Clin Transl Immunology. 2021 Apr 5;10(4):e1269. doi: 10.1002/cti2.1269. eCollection 2021.

Authors

Daniel Watterson^{1

2

3}, Danushka K Wijesundara^{1

2}, Naphak Modhiran^{1

2}, Francesca L Mordant⁴, Zheyi Li⁵, Michael S Avumegah^{1

2}, Christopher Ld McMillan^{1

2}, Julia Lackenby^{1

2}, Kate Guilfoyle⁶, Geert van Amerongen⁶, Koert Stittelaar⁶, Stacey Tm Cheung¹, Summa Bibby¹, Mallory Daleris², Kym Hoger², Marianne Gillard², Eve Radunz², Martina L Jones², Karen Hughes², Ben Hughes², Justin Goh², David Edwards², Judith Scoble⁷, Lesley Pearce⁷, Lukasz Kowalczyk⁷, Tram Phan⁷, Mylinh La⁷, Louis Lu⁷, Tam Pham⁷, Qi Zhou⁷, David A Brockman⁸, Sherry J Morgan⁹, Cora Lau¹⁰, Mai H Tran⁸, Peter Tapley⁸, Fernando Villalón-Letelier⁴, James Barnes¹¹, Andrew Young^{1

2}, Noushin Jaberolansar^{1

2}, Connor Ap Scott¹, Ariel Isaacs¹, Alberto A Amarilla¹, Alexander A Khromykh^{1

3}, Judith Ma van den Brand¹², Patrick C Reading^{4

11}, Charani Ranasinghe⁵, Kanta Subbarao^{4

11}, Trent P Munro^{1

2}, Paul R Young^{1

2

3}, Keith J Chappell^{1

2

3}

Affiliations

¹ School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
² The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
³ Australian Infectious Disease Research Centre, Global Virus Network Centre of Excellence The University of Queensland Brisbane QLD Australia.
⁴ Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
⁵ Department of Immunology and Infectious Disease The John Curtin School of Medical Research, The Australian National University Canberra ACT Australia.
⁶ Viroclinics Xplore Schaijk The Netherlands.
⁷ CSIRO Manufacturing Parkville VIC Australia.
⁸ TetraQ The University of Queensland St Lucia QLD Australia.
⁹ StageBio Mason OH USA.
¹⁰ University of Queensland Biological Resources The University of Queensland St Lucia QLD Australia.
¹¹ WHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
¹² Division of Pathology Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands.

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.

Keywords: Molecular Clamp; SARS‐CoV‐2; neutralising antibodies; polyfunctional T cells; rapid response; subunit vaccine.