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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: Bewley, K.R. ORCID logoORCID: https://orcid.org/0000-0002-9078-6734, Gooch, K., Thomas, K.M. ORCID logoORCID: https://orcid.org/0000-0002-0348-654X, Longet, S., Wiblin, N., Hunter, L., Chan, K., Brown, P. ORCID logoORCID: https://orcid.org/0000-0001-6367-6495, Russell, R. A. ORCID logoORCID: https://orcid.org/0000-0002-6517-6483, Ho, C., Slack, G., Humphries, H.E. ORCID logoORCID: https://orcid.org/0000-0003-2576-8502, Alden, L., Allen, L. ORCID logoORCID: https://orcid.org/0000-0003-1846-8181, Aram, M. ORCID logoORCID: https://orcid.org/0000-0002-2413-9862, Baker, N., Brunt, E., Cobb, R., Fotheringham, S., Harris, D., Kennard, C., Leung, S. ORCID logoORCID: https://orcid.org/0000-0002-8880-2977, Ryan, K. ORCID logoORCID: https://orcid.org/0000-0001-8608-1144, Tolley, H., Wand, N., White, A. ORCID logoORCID: https://orcid.org/0000-0001-9481-0079, Sibley, L. ORCID logoORCID: https://orcid.org/0000-0002-4188-3423, Sarfas, C. ORCID logoORCID: https://orcid.org/0000-0001-9056-0308, Pearson, G., Rayner, E., Xue, X., Lambe, T. ORCID logoORCID: https://orcid.org/0000-0001-7711-897X, Charlton, S., Gilbert, S. ORCID logoORCID: https://orcid.org/0000-0002-6823-9750, Sattentau, Q.J. ORCID logoORCID: https://orcid.org/0000-0001-7170-1937, Gleeson, F., Hall, Y. ORCID logoORCID: https://orcid.org/0000-0002-8537-8920, Funnell, S., Sharpe, S., Salguero, F.J., Gorringe, A. ORCID logoORCID: https://orcid.org/0000-0003-2193-7954 and Carroll, M. ORCID logoORCID: https://orcid.org/0000-0002-7026-7187
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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