1. Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques
- Author
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Sally Sharpe, Leonie Alden, Laura Sibley, Charlotte Sarfas, Sarah C. Gilbert, Karen E. Gooch, Catherine M K Ho, Francisco J. Salguero, Emma Rayner, Holly E. Humphries, Quentin J. Sattentau, Simon G. P. Funnell, Teresa Lambe, Stephanie Longet, Nathan R Wiblin, Stephanie Leung, Chelsea L Kennard, Rebecca Cobb, Laura Hunter, Fergus V. Gleeson, Rebecca A. Russell, Marilyn Aram, Howard Tolley, Phillip Brown, Emily Brunt, Sue Charlton, Nadina Wand, Andrew White, Susan A. Fotheringham, Kin Chan, Geoff Pearson, Xiaochao Xue, Andrew Gorringe, Miles W. Carroll, Natalie Baker, Lauren Allen, Kevin R. Bewley, Kathryn A. Ryan, Debbie J Harris, Gillian S. Slack, Yper Hall, and Kelly M. Thomas
- Subjects
Coronavirus disease 2019 (COVID-19) ,business.industry ,viruses ,Viral Vaccine ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,virus diseases ,Disease ,biochemical phenomena, metabolism, and nutrition ,respiratory system ,medicine.disease_cause ,Virology ,Immunity ,Inactivated vaccine ,medicine ,business ,Pathological ,Coronavirus - Abstract
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.
- Published
- 2020