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


  • K.R. Bewley
  • K. Gooch
  • K.M. Thomas
  • S. Longet
  • N. Wiblin
  • L. Hunter
  • K. Chan
  • P. Brown
  • R. A. Russell
  • C. Ho
  • G. Slack
  • H.E. Humphries
  • L. Alden
  • L. Allen
  • M. Aram
  • N. Baker
  • E. Brunt
  • R. Cobb
  • S. Fotheringham
  • D. Harris
  • C. Kennard
  • S. Leung
  • K. Ryan
  • H. Tolley
  • N. Wand
  • A. White
  • L. Sibley
  • C. Sarfas
  • G. Pearson
  • E. Rayner
  • X. Xue
  • T. Lambe
  • S. Charlton
  • S. Gilbert
  • Q.J. Sattentau
  • F. Gleeson
  • Y. Hall
  • S. Funnell
  • S. Sharpe
  • F.J. Salguero
  • A. Gorringe
  • M. Carroll


  • Science Advances


  • Sci Adv 7 (37): eabg7996


  • 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.