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.
Highlights
A new tick-borne disease, Crimean Haemorrhagic Fever, was first described in the Crimea in 1945 [1]
We aimed to develop a candidate vaccine based on recombinant Modified Vaccinia virus Ankara (MVA) expressing the CCHF virus (CCHFv) glycoproteins, to assess the induction of cellular and humoral immunity, and to evaluate efficacy in a challenge model that represents human disease
The glycoprotein was fused to the signal sequence of tissue plasminogen activator (tPA) at the amino-terminus for increased immunogenicity and intracellular transport [36,37]
Summary
A new tick-borne disease, Crimean Haemorrhagic Fever, was first described in the Crimea in 1945 [1]. In 1969 it was recognised that the virus causing the disease was identical to a virus isolated in the Congo in 1956 [2], and the disease was subsequently renamed Crimean-Congo Haemorrhagic Fever (CCHF). The causative agent, CCHF virus (CCHFv), is a member of the Nairovirus genus in the Bunyaviridae family. The most efficient and common tick vectors appear to be members of the Hyalomma genus, which commonly infest livestock and other animals. CCHF causes a severe human disease, with a fatality rate of 15–70% [3]. Detectable antibody responses are usually required for survival, but are not predictive of recovery [6]. It is likely that both antibody and CD8-positive T lymphocytes are required for protection
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