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

Kevin R. Bewley, Karen Gooch, Kelly M. Thomas, Stephanie Longet, Nathan Wiblin, Laura Hunter, Kin Chan, Phillip Brown, Rebecca A. Russell, Catherine Ho, Gillian Slack, Holly E. Humphries, Leonie Alden, Lauren Allen, Marilyn Aram, Natalie Baker, Emily Brunt, Rebecca Cobb, Susan Fotheringham, Debbie HarrisChelsea Kennard, Stephanie Leung, Kathryn Ryan, Howard Tolley, Nadina Wand, Andrew White, Laura Sibley, Charlotte Sarfas, Geoff Pearson, Emma Rayner, Xiaochao Xue, Teresa Lambe, Sue Charlton, Sarah Gilbert, Quentin J. Sattentau, Fergus Gleeson, Yper Hall, Simon Funnell, Sally Sharpe, Francisco J. Salguero, Andrew Gorringe*, Miles Carroll

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number7996
Number of pages17
JournalScience Advances
Issue number37
Publication statusPublished - Sep 2021

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