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Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.
Saunders, Jack E; Gilbride, Ciaran; Dowall, Stuart; Morris, Susan; Ulaszewska, Marta; Spencer, Alexandra J; Rayner, Emma; Graham, Victoria A; Kennedy, Emma; Thomas, Kelly; Hewson, Roger; Gilbert, Sarah C; Belij-Rammerstorfer, Sandra; Lambe, Teresa.
Affiliation
  • Saunders JE; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: jack.saunders@univ.ox.ac.uk.
  • Gilbride C; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dowall S; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Morris S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ulaszewska M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Spencer AJ; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Rayner E; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Graham VA; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Kennedy E; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Thomas K; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Hewson R; UK Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, UK.
  • Gilbert SC; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Belij-Rammerstorfer S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: sandra.belij-rammerstorfer@paediatrics.ox.ac.uk.
  • Lambe T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.
EBioMedicine ; 90: 104523, 2023 Apr.
Article in En | MEDLINE | ID: mdl-36933409
ABSTRACT

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].
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Viral Vaccines / Hemorrhagic Fever Virus, Crimean-Congo / Hemorrhagic Fever, Crimean Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: EBioMedicine Year: 2023 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Viral Vaccines / Hemorrhagic Fever Virus, Crimean-Congo / Hemorrhagic Fever, Crimean Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: EBioMedicine Year: 2023 Document type: Article