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Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques
Item Type: | Article |
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Title: | Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques |
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Creators Name: | Bewley, K.R. and Gooch, K. and Thomas, K.M. and Longet, S. and Wiblin, N. and Hunter, L. and Chan, K. and Brown, P. and Russell, R. A. and Ho, C. and Slack, G. and Humphries, H.E. and Alden, L. and Allen, L. and Aram, M. and Baker, N. and Brunt, E. and Cobb, R. and Fotheringham, S. and Harris, D. and Kennard, C. and Leung, S. and Ryan, K. and Tolley, H. and Wand, N. and White, A. and Sibley, L. and Sarfas, C. and Pearson, G. and Rayner, E. and Xue, X. and Lambe, T. and Charlton, S. and Gilbert, S. and Sattentau, Q.J. and Gleeson, F. and Hall, Y. and Funnell, S. and Sharpe, S. and Salguero, F.J. and Gorringe, A. and Carroll, M. |
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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. |
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Keywords: | Animals, Mustela putorius furo, Macaca mulatta |
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Source: | Science Advances |
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ISSN: | 2375-2548 |
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Publisher: | American Association for the Advancement of Science |
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Volume: | 7 |
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Number: | 37 |
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Page Range: | eabg7996 |
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Date: | 10 September 2021 |
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Official Publication: | https://doi.org/10.1126/sciadv.abg7996 |
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PubMed: | View item in PubMed |
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