scholarly journals Crimean-Congo Hemorrhagic Fever Virus (CCHFV): A Silent but Widespread Threat

2021 ◽  
Author(s):  
Paul A. Kuehnert ◽  
Christopher P. Stefan ◽  
Catherine V. Badger ◽  
Keersten M. Ricks
Keyword(s):  
One Health ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Virus Vector ◽  
Disease Spread ◽  
Fatality Rate ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
High Fatality Rate ◽  
Endemic Areas

Abstract Purpose of Review This review is aimed at highlighting recent research and articles on the complicated relationship between virus, vector, and host and how biosurveillance at each level informs disease spread and risk. Recent Findings While human cases of CCHFV and tick identification in non-endemic areas in 2019–2020 were reported to sites such as ProMed, there is a gap in recent published literature on these and broader CCHFV surveillance efforts from the late 2010s. Summary A review of the complex aspects of CCHFV maintenance in the environment coupled with high fatality rate and lack of vaccines and therapeutics warrants the need for a One-Health approach toward detection and increased biosurveillance programs for CCHFV.

scholarly journals Nucleoside-modified mRNA vaccines protect IFNAR -/- mice against Crimean Congo hemorrhagic fever virus infection

2021 ◽  
Author(s):  
Sofia Appelberg ◽  
Lijo John ◽  
Norbert Pardi ◽  
Ákos Végvári ◽  
Sándor Bereczky ◽  
...  
Keyword(s):  
Immune Response ◽  
Global Health ◽  
Immune Responses ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Fatality Rate ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
High Fatality Rate ◽  
The World

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations’ list of prioritized diseases and pathogens. With global distribution, high fatality rate and no approved vaccine or effective treatment, CCHF constitutes a threat against global health. In the current study, we demonstrate that vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNP), encoding for the CCHFV nucleoprotein (N) or glycoproteins (GcGn) protect IFNAR -/- mice against lethal CCHFV infection. In addition, we found that both mRNA-LNP induced strong humoral and cellular immune responses in IFNAR -/- and immunocompetent mice and that neutralizing antibodies are not necessary for protection. When evaluating immune responses induced by immunization including CCHFV Gc and Gn antigens, we found the Gc protein to be more immunogenic compared to the Gn protein. Hepatic injury is prevalent in CCHF and contributes to the severity and mortality of the disease in humans. Thus, to understand the immune response in the liver after infection and the potential effect of the vaccine, we performed a proteomic analysis on liver samples from vaccinated and control mice after CCHFV infection. Similar to observations in humans, vaccination affected the metabolic pathways. In conclusion, this study shows that a CCHFV mRNA-LNP vaccine, based on viral nucleo- or glycoproteins, mediate protection against CCHFV induced disease. Consequently, genetic immunization is an attractive approach to prevent disease caused by CCHFV and we believe we have necessary evidence to bring this vaccine platform to the next step in the development of a vaccine against CCHFV infection. Importance Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic pathogen causing Crimean-Congo hemorrhagic fever (CCHF), a severe fever disease. CCHFV have a wide distribution and are endemic in several areas around the world. Cases of CCHF are also being reported in new areas, indicating an expansion of the disease, which is of high concern. Dispersion of the disease, high fatality rate and no approved vaccine makes CCHF a threat to global health. The development of a vaccine is thus of great importance. Here we show 100% protection against lethal CCHFV infection in mice immunized with mRNA-LNP encoding for different CCHFV proteins. The vaccination showed both robust humoral and cellular immunity. mRNA-LNP vaccines combine the ability to induce an effective immune response, the safety of a transient carrier and the flexibility of genetic vaccines. This and our results from the current study support the development of a mRNA-LNP based vaccine against CCHFV.

BSL4 Facilities in Anti-Infectious Disease Measures

2009 ◽  
Vol 4 (5) ◽  
pp. 352-355 ◽  
Author(s):  
Ichiro Kurane ◽  
Keyword(s):  
Infectious Disease ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Lassa Virus ◽  
South American ◽  
Environment Effect ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Multiple Factors ◽  
Endemic Areas

Pathogens are divided into biosafety levels (BSL) 1 to 4 based on multiple factors such as virulence, transmissibility, environment effect, and treatment availability. BSL1 pathogens are the least virulent and BSL4 the most. BSL4 pathogens include ebolavirus, marburgvirus, Crimean-Congo hemorrhagic fever virus, lassa virus, variolla virus, and South American hemorrhagic fever viruses, as detailed in Table 1. Pathogens at each of the 4 BSLs must be handled in equivalently physically contained laboratories, graded P1-4. BSL4 pathogens do not exist in nature in Japan, which currently has no equivalent physical containment facilities, but the possibility exists that they may be brought into the country unintentionally by those infected in endemic areas or intentionally by bioterrorists.

scholarly journals Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1491
Author(s):  
Thomas Tipih ◽  
Mark Heise ◽  
Felicity Jane Burt
Keyword(s):  
Immune Response ◽  
Sindbis Virus ◽  
Cytokine Production ◽  
Antiviral Drug ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Virus Vector ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

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.

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