| Autor: |
Francesca L Mordant, Danushka K. Wijesundara, Keith J. Chappell, Cora Lau, Naphak Modhiran, Kanta Subbarao, Stacey T. M. Cheung, Ariel Isaacs, Charani Ranasinghe, Julia Lackenby, Martina L. Jones, Qi Zhou, Eve Radunz, James G. Barnes, Kate Guilfoyle, Koert J. Stittelaar, Zheyi Li, Peter Tapley, Justin B. Goh, Tram Phan, Karen Hughes, Judith M. A. van den Brand, Noushin Jaberolansar, Benjamin S. Hughes, Sherry J. Morgan, Connor A. P. Scott, Judith A. Scoble, Trent P. Munro, Tam Pham, Patrick C. Reading, Mai H. Tran, Andrew Young, Fernando Villalón-Letelier, Marianne Gillard, Lesley A. Pearce, Michael S. Avumegah, Mylinh La, Summa Bibby, Christopher L. D. McMillan, Daniel Watterson, Lukasz Kowalczyk, Mallory Daleris, Paul R. Young, Louis Lu, Alberto A. Amarilla, Alexander A. Khromykh, David Edwards, Kym Hoger, Geert van Amerongen, David A. Brockman |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| Popis: |
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. This strategy uses an orthogonal stabilisation approach compared to canonical vaccines, in combination with the licensed adjuvant MF59 (Seqirus). 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. The Sclamp vaccine candidate is currently completing Phase 1 clinical evaluation, in parallel with large-scale commercial manufacture for pivotal efficacy trials and potential widespread distribution. Funding: This work was funded by CEPI. Conflict of Interest: K.J.C., D.W. and P.R.Y. are inventors of the “Molecular Clamp” patent, US 2020/0040042. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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