| Autor: |
Ariel Isaacs, Naphak Modhiran, James G. Barnes, Christopher L. D. McMillan, Koert J. Stittelaar, Tram Phan, Patrick C. Reading, Geert van Amerongen, Francesca L Mordant, Stacey T. M. Cheung, Connor Scott, Eve Radunz, Daniel Watterson, Louis Lu, Alberto A. Amarilla, Lukasz Kowalczyk, Mai Tran, Mallory Daleris, David A. Brockman, Marianne Gillard, Sherry J. Morgan, Zheyi Li, Noushin Jaberolansar, Julia Lackenby, Michael S. Avumegah, David Edwards, Kym Hoger, Karen Hughes, Judith A. Scoble, Charani Ranasinghe, Qi Zhou, Danushka K. Wijesundara, Fernando Villalon Letelier, Martina L. Jones, Ben Hughes, Kanta Subbarao, Mylinh La, Keith J. Chappell, Summa Bibby, Peter Tapley, Andrew Young, Cora Lau, Lesley A. Pearce, Tam Pham, Trent P. Munro, Paul R. Young, Alexander A. Khromykh, Justin B. Goh, Kate Guilfoyle |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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