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Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques
Kevin R Bewley; Karen E R Gooch; Kelly M Thomas; Stephanie R 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 A Ryan; Howard Tolley; Nadina Wand; Andrew White; Laura Sibley; Charlotte Sarfas; Geoff Pearson; Emma Rayner; Xiaochao Xue; Teresa Lambe; Sue Charlton; Sarah C Gilbert; Quentin Sattentau; Fergus Gleeson; Yper Hall; Simon G. P. Funnell; Sally Sharpe; Francisco Javier Salguero; Andrew R Gorringe; Miles Carroll.
Afiliación
  • Kevin R Bewley; Public Health England, Porton Down
  • Karen E R Gooch; Public Health England
  • Kelly M Thomas; Public Health England, Porton Down
  • Stephanie R Longet; Public Health England, Porton Down
  • Nathan Wiblin; Public Health England, Porton Down
  • Laura Hunter; Public Health England, Porton Down
  • Kin Chan; Public Health England, Porton Down
  • Phillip Brown; Public Health England, Porton Down
  • Rebecca A Russell; Public Health England, Porton Down
  • Catherine Ho; Public Health England, Porton Down
  • Gillian Slack; Public Health England, Porton Down
  • Holly E Humphries; Public Health England, Porton Down
  • Leonie Alden; Public Health England, Porton Down
  • Lauren Allen; Public Health England, Porton Down
  • Marilyn Aram; Public Health England, Porton Down
  • Natalie Baker; Public Health England, Porton Down
  • Emily Brunt; Public Health England, Porton Down
  • Rebecca Cobb; Public Health England, Porton Down
  • Susan Fotheringham; Public Health England, Porton Down
  • Debbie Harris; Public Health England, Porton Down
  • Chelsea Kennard; Public Health England, Porton Down
  • Stephanie Leung; Public Health England, Porton Down
  • Kathryn A Ryan; Public Health England, Porton Down
  • Howard Tolley; Public Health England, Porton Down
  • Nadina Wand; Public Health England, Porton Down
  • Andrew White; Public Health England, Porton Down
  • Laura Sibley; Public Health England, Porton Down
  • Charlotte Sarfas; Public Health England, Porton Down
  • Geoff Pearson; Public Health England, Porton Down
  • Emma Rayner; Public Health England, Porton Down
  • Xiaochao Xue; The Sir William Dunn School of Pathology, University of Oxford
  • Teresa Lambe; The Jenner Institute, University of Oxford
  • Sue Charlton; Public Health England, Porton Down
  • Sarah C Gilbert; University of Oxford
  • Quentin Sattentau; The Sire William Dunn School of Pathology, University of Oxford
  • Fergus Gleeson; Oxford Departments of Radiology and Nuclear Medicine, Oxford University Hospitals NHS Foundation Trust.
  • Yper Hall; Public Health England, Porton Down
  • Simon G. P. Funnell; Public Health England, Porton Down
  • Sally Sharpe; Public Health England, Porton Down
  • Francisco Javier Salguero; Public Health England, Porton Down
  • Andrew R Gorringe; Public Health England, Porton Down
  • Miles Carroll; Public Health England, Porton Down
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-423746
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.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint