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


Date: 21st December 2020 | Source: BioRxiv

Authors: 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 Harris, Chelsea 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.

There is an urgent requirement for safe and effective vaccines to prevent novel coronavirus disease (COVID-19) caused by SARS-CoV-2. 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 ferret 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 in ferrets or unvaccinated macaques. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen at seven days post infection in ferrets. This increased lung pathology was observed early in the infection (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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