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

KR Bewley, K Gooch, KM Thomas, S Longet… - Science …, 2021 - science.org
KR Bewley, K Gooch, KM Thomas, S Longet, N Wiblin, L Hunter, K Chan, P Brown…
Science advances, 2021science.org
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 …
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.
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