Clin Transl Immunology
. 2021 Apr 5;10(4):e1269.
doi: 10.1002/cti2.1269. eCollection 2021.
Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
Daniel Watterson 1 2 3 , Danushka K Wijesundara 1 2 , Naphak Modhiran 1 2 , Francesca L Mordant 4 , Zheyi Li 5 , Michael S Avumegah 1 2 , Christopher Ld McMillan 1 2 , Julia Lackenby 1 2 , Kate Guilfoyle 6 , Geert van Amerongen 6 , Koert Stittelaar 6 , Stacey Tm Cheung 1 , Summa Bibby 1 , Mallory Daleris 2 , Kym Hoger 2 , Marianne Gillard 2 , Eve Radunz 2 , Martina L Jones 2 , Karen Hughes 2 , Ben Hughes 2 , Justin Goh 2 , David Edwards 2 , Judith Scoble 7 , Lesley Pearce 7 , Lukasz Kowalczyk 7 , Tram Phan 7 , Mylinh La 7 , Louis Lu 7 , Tam Pham 7 , Qi Zhou 7 , David A Brockman 8 , Sherry J Morgan 9 , Cora Lau 10 , Mai H Tran 8 , Peter Tapley 8 , Fernando Villal?n-Letelier 4 , James Barnes 11 , Andrew Young 1 2 , Noushin Jaberolansar 1 2 , Connor Ap Scott 1 , Ariel Isaacs 1 , Alberto A Amarilla 1 , Alexander A Khromykh 1 3 , Judith Ma van den Brand 12 , Patrick C Reading 4 11 , Charani Ranasinghe 5 , Kanta Subbarao 4 11 , Trent P Munro 1 2 , Paul R Young 1 2 3 , Keith J Chappell 1 2 3
Affiliations
- PMID: 33841880
- PMCID: PMC8021130
- DOI: 10.1002/cti2.1269
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.