title: A novel vaccine against Crimean-Congo Haemorrhagic Fever protects 100% of animals against lethal challenge in a mouse model.
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.
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Buttigieg
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Dowall
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Findlay-Wilson
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Miloszewska
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
authors.affiliation: Microbiology Services Research, Public Health England, Porton Down, Wiltshire, United Kingdom.
authors.forename: Miles W
authors.initials: MW
authors.lastname: Carroll
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004274:DNA, Recombinant / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology / Q000502:physiology; D006479:Hemorrhagic Fever, Crimean / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D010957:Plasmids / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D017471:Receptors, Interferon / Q000172:deficiency; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D004274:DNA, Recombinant; D006023:Glycoproteins; D017471:Receptors, Interferon; D014764:Viral Proteins; D014765:Viral Vaccines; C120411:interferon receptor, type II; D053633:Receptor, Interferon alpha-beta