Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Bewley, K.R.; Gooch, K.; Thomas, K.M.; Longet, S.; Wiblin, N.; Hunter, L.; Chan, K.; Brown, P.; Russell, R. A.; Ho, C.; Slack, G.; Humphries, H.E.; Alden, L.; Allen, L.; Aram, M.; Baker, N.; Brunt, E.; Cobb, R.; Fotheringham, S.; Harris, D.; Kennard, C.; Leung, S.; Ryan, K.; Tolley, H.; Wand, N.; White, A.; Sibley, L.; Sarfas, C.; Pearson, G.; Rayner, E.; Xue, X.; Lambe, T.; Charlton, S.; Gilbert, S.; Sattentau, Q.J.; Gleeson, F.; Hall, Y.; Funnell, S.; Sharpe, S.; Salguero, F.J.; Gorringe, A.; Carroll, M.

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

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Item Type:	Article
Title:	Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques
Creators Name:	Bewley, K.R., Gooch, K., Thomas, K.M., Longet, S., Wiblin, N., Hunter, L., Chan, K., Brown, P., Russell, R. A., Ho, C., Slack, G., Humphries, H.E., Alden, L., Allen, L., Aram, M., Baker, N., Brunt, E., Cobb, R., Fotheringham, S., Harris, D., Kennard, C., Leung, S., Ryan, K., Tolley, H., Wand, N., White, A., Sibley, L., Sarfas, C., Pearson, G., Rayner, E., Xue, X., Lambe, T., Charlton, S., Gilbert, S., Sattentau, Q.J., Gleeson, F., Hall, Y., Funnell, S., Sharpe, S., Salguero, F.J., Gorringe, A. and Carroll, M.
Abstract:	There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.
Keywords:	Animals, Mustela putorius furo, Macaca mulatta
Source:	Science Advances
ISSN:	2375-2548
Publisher:	American Association for the Advancement of Science
Volume:	7
Number:	37
Page Range:	eabg7996
Date:	10 September 2021
Official Publication:	https://doi.org/10.1126/sciadv.abg7996
PubMed:	View item in PubMed

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