Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2. Issue 4 (5th April 2021)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: Clinical & translational immunology. Volume 10:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-04-05
• Subjects: Molecular Clamp -- neutralising antibodies -- polyfunctional T cells -- rapid response -- SARS‐CoV‐2 -- subunit vaccine; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1269
• Languages: English
• ISSNs: 2050-0068

Abstract

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. Abstract : We describe preclinical development of a prefusion stabilized spike protein subunit vaccine for SARS‐CoV‐2. Results include structural resolution by cryo‐electron microscopy, mouse immunogenicity and a hamster protection study.