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Efficacy and potential human and economic impact of a broadly protective betacoronavirus vaccine

Carnell, G. W.; Vendramelli, R.; Whittaker, C. W.; Holbrook, J.; Parthasarathy, S.; Stewart, H.; Olivier, J.; Warner, B.; Truong, T.; George, C.; Sujit, S. B.; Ashokan, S.; Suau Sans, M.; Huang, C. Q.; Wells, D. A.; Tonks, P.; Pfranger, M.; Einhauser, S.; Neckermann, P.; Cantoni, D.; Chan, A. C. Y.; O'Reilly, L.; Ohlendorf, L.; Unwins, I.; Rautenbach, S.; Ferrari, M.; Firth, A.; Geiger, J.; Dohmen, C.; Mummert, V.; Samuel, A. R.; Plank, C.; Del Rosario, J.; Temperton, N. J.; Asbach, B.; Frost, S. D. W.; Kinsley, R.; Vishwanath, S.; Fedosyuk, S.; Wagner, R.; Kobasa, D.; Heeney, J. L.

2025-10-19 infectious diseases
10.1101/2025.10.17.25338244 medRxiv
Show abstract

Within two decades, three different betacoronaviruses ({beta}-CoV) have spilled over from animals to humans causing high consequence diseases, the most recent causing the COVID-19 pandemic. Using computational antigen design technology, we developed a single multivalent vaccine candidate capable of broadly neutralising diverse animal and human {beta}-CoVs. We then demonstrated that this single vaccine could protect mice from lethal infection against the three genetically distinct human SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Epidemiological modelling revealed that a single broadly protective {beta}-CoV vaccine (BPBV) of moderate efficacy (50% against severe disease) could have averted a significant fraction of deaths during the SARS-CoV-2 pandemic, depending on the degree of clinical preparedness established pre-pandemic. Deaths averted by the BPBV varied in our simulations, ranging from 47% if the BPBV had been clinically evaluated through to a phase 2 trail, and ready for vaccine efficacy trials early during an initial outbreak, to 13% if phase 1 clinical testing of such a BPBV had not yet been initiated. Taken together we provide pre-clinical evidence of robust efficacy of a single BPBV vaccine candidate and modelling data demonstrating the significant positive impact on human health and significant economic benefit to national economies which would be achieved by clinically advancing and stockpiling a Phase 3 ready BPBV vaccine in the event of new virus outbreaks.

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