A novel vaccine against Crimean-Congo Haemorrhagic Fever protects 100% of animals against lethal challenge in a mouse model

Karen R Buttigieg; Stuart D Dowall; Stephen Findlay-Wilson; Aleksandra Miloszewska; Emma Rayner; Roger Hewson; Miles W Carroll

doi:10.1371/journal.pone.0091516

A novel vaccine against Crimean-Congo Haemorrhagic Fever protects 100% of animals against lethal challenge in a mouse model

PLoS One. 2014 Mar 12;9(3):e91516. doi: 10.1371/journal.pone.0091516. eCollection 2014.

Authors

Karen R Buttigieg¹, Stuart D Dowall¹, Stephen Findlay-Wilson¹, Aleksandra Miloszewska¹, Emma Rayner¹, Roger Hewson¹, Miles W Carroll¹

Affiliation

¹ Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.

Abstract

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cricetinae
DNA, Recombinant / genetics
Disease Models, Animal
Female
Glycoproteins / genetics
Glycoproteins / immunology
Hemorrhagic Fever Virus, Crimean-Congo / immunology
Hemorrhagic Fever Virus, Crimean-Congo / physiology
Hemorrhagic Fever, Crimean / immunology
Hemorrhagic Fever, Crimean / metabolism
Hemorrhagic Fever, Crimean / pathology
Hemorrhagic Fever, Crimean / prevention & control*
Immunity, Cellular
Immunity, Humoral
Mice
Plasmids / genetics
Receptor, Interferon alpha-beta / deficiency
Receptors, Interferon / deficiency
Viral Load
Viral Proteins / genetics
Viral Proteins / immunology
Viral Vaccines / genetics
Viral Vaccines / immunology*

Substances

DNA, Recombinant
Glycoproteins
Receptors, Interferon
Viral Proteins
Viral Vaccines
interferon receptor, type II
Receptor, Interferon alpha-beta

Grants and funding

This work was funded by the Health Protection Agency (subsequently part of Public Health England) of the United Kingdom. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.