Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean-Congo Hemorrhagic Fever Virus Nucleoprotein.

Thomas Tipih,Felicity Jane Burt,Mark Heise

doi:10.3390/vaccines9121491

Abstract

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

Highlights

Crimean–Congo hemorrhagic fever virus (CCHFV) exclusively causes disease in humans
Our experiments demonstrated the capacity of the Sindbis replicons to direct the expression of the CCHFV nucleocapsid protein (NP) in vitro
We reported the preparation of a Sindbis replicon expressing the full-length open reading frame of a CCHFV NP from a South African isolate

Summary

Introduction

Crimean–Congo hemorrhagic fever virus (CCHFV) exclusively causes disease in humans. The virus has an extensive global geographic distribution, and the disease has been reported in a wide array of countries in Africa, Asia, the Middle East, Eastern Europe and recently in Spain, Western Europe [1,2,3,4]. A total of seven human cases have been reported in Spain from 2016 to August 2020, with a case fatality rate of 42.9% [5]. Data from the Spanish studies indicate an establishment of the CCHFV transmission cycle in the country [5]. CCHFV is maintained in a life cycle involving ticks and vertebrate animals [1], while humans are regarded as incidental hosts. Infections are associated with the hemorrhagic syndrome, with a mortality rate of 30%

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Conclusion