Open AccessPreclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
Author(s) -
Watterson Daniel,
Wijesundara Danushka K,
Modhiran Naphak,
Mordant Francesca L,
Li Zheyi,
Avumegah Michael S,
McMillan Christopher LD,
Lackenby Julia,
Guilfoyle Kate,
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,
VillalónLetelier Fernando,
Barnes James,
Young Andrew,
Jaberolansar Noushin,
Scott Connor AP,
Isaacs Ariel,
Amarilla Alberto A,
Khromykh Alexander A,
Brand Judith MA,
Reading Patrick C,
Ranasinghe Charani,
Subbarao Kanta,
Munro Trent P,
Young Paul R,
Chappell Keith J
Publication year - 2021
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1269
Subject(s) - coronavirus , protein subunit , virology , covid-19 , medicine , respiratory system , immunology , biology , gene , genetics , disease , infectious disease (medical specialty) , outbreak
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.