PT  - JOURNAL ARTICLE
AU  - Kevin R. Bewley
AU  - Karen Gooch
AU  - Kelly M. Thomas
AU  - Stephanie Longet
AU  - Nathan Wiblin
AU  - Laura Hunter
AU  - Kin Chan
AU  - Phillip Brown
AU  - Rebecca A. Russell
AU  - Catherine Ho
AU  - Gillian Slack
AU  - Holly E. Humphries
AU  - Leonie Alden
AU  - Lauren Allen
AU  - Marilyn Aram
AU  - Natalie Baker
AU  - Emily Brunt
AU  - Rebecca Cobb
AU  - Susan Fotheringham
AU  - Debbie Harris
AU  - Chelsea Kennard
AU  - Stephanie Leung
AU  - Kathryn Ryan
AU  - Howard Tolley
AU  - Nadina Wand
AU  - Andrew White
AU  - Laura Sibley
AU  - Charlotte Sarfas
AU  - Geoff Pearson
AU  - Emma Rayner
AU  - Xiaochao Xue
AU  - Teresa Lambe
AU  - Sue Charlton
AU  - Sarah Gilbert
AU  - Quentin J. Sattentau
AU  - Fergus Gleeson
AU  - Yper Hall
AU  - Simon Funnell
AU  - Sally Sharpe
AU  - Francisco J. Salguero
AU  - Andrew Gorringe
AU  - Miles Carroll
TI  - Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques
AID  - 10.1101/2020.12.21.423746
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.21.423746
4099  - http://biorxiv.org/content/early/2020/12/21/2020.12.21.423746.short
4100  - http://biorxiv.org/content/early/2020/12/21/2020.12.21.423746.full
AB  - 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.Competing Interest StatementSarah Gilbert and Teresa Lambe are named on a patent application covering a vaccine ChAdOx1 nCoV-19. The remaining authors declare no competing interests.