Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
Watterson, Daniel; Wijesundara, Danushka K; Modhiran, Naphak; Mordant, Francesca L; Li, Zheyi; Avumegah, Michael S; McMillan, Christopher Ld; Lackenby, Julia; Guilfoyle, Kate; van Amerongen, Geert; Stittelaar, Koert; Cheung, Stacey Tm; Bibby, Summa; Daleris, Mallory; Hoger, Kym; Gillard, Marianne; Radunz, Eve; Jones, Martina L; Hughes, Karen; Hughes, Ben; Goh, Justin; Edwards, David; Scoble, Judith; Pearce, Lesley; Kowalczyk, Lukasz; Phan, Tram; La, Mylinh; Lu, Louis; Pham, Tam; Zhou, Qi; Brockman, David A; Morgan, Sherry J; Lau, Cora; Tran, Mai H; Tapley, Peter; Villalón-Letelier, Fernando; Barnes, James; Young, Andrew; Jaberolansar, Noushin; Scott, Connor Ap; Isaacs, Ariel; Amarilla, Alberto A; Khromykh, Alexander A; van den Brand, Judith Ma; Reading, Patrick C; Ranasinghe, Charani; Subbarao, Kanta; Munro, Trent P; Young, Paul R; Chappell, Keith J
(2021) Utrecht University Repository
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:
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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.
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