Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge modelResearch in context
Jack E. Saunders,
Ciaran Gilbride,
Stuart Dowall,
Susan Morris,
Marta Ulaszewska,
Alexandra J. Spencer,
Emma Rayner,
Victoria A. Graham,
Emma Kennedy,
Kelly Thomas,
Roger Hewson,
Sarah C. Gilbert,
Sandra Belij-Rammerstorfer,
Teresa Lambe
Affiliations
Jack E. Saunders
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Corresponding author.
Ciaran Gilbride
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Stuart Dowall
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Susan Morris
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Marta Ulaszewska
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Alexandra J. Spencer
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Emma Rayner
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Victoria A. Graham
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Emma Kennedy
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Kelly Thomas
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Roger Hewson
UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK
Sarah C. Gilbert
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Sandra Belij-Rammerstorfer
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Corresponding author. Oxford Vaccine Group, IMS-Tetsuya Nakamura Building, Roosevelt Dr, OX3 7TY, Oxford, UK.
Teresa Lambe
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK
Summary: Background: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage. Methods: In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV. Findings: We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease. Interpretation: There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV. Funding: This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].
