Abstract
Development of new vaccine platforms against viral diseases is considered urgent. In recent years, mRNA constructs have attracted great interest in this field due to unique advantages over conventional gene transfer platforms. In the present study, we developed a new naked conventional mRNA vaccine expressing the non-optimized small (S) segment of the Ank-2 strain of Crimean-Congo Hemorrhagic Fever virus (CCHFV). We then analyzed its single and booster dose immunogenicity and protection potential in the challenge assay in two mice models, including IFNα/β/γR−/− and C57BL/6. The results obtained from the immunological assays, namely IL-4 and IFN-gamma ELISPOT, intracellular IFN-gamma staining, in-house sandwich ELISA, and survival data, demonstrated that our construct elicited the production of anti-nucleocapsid (N) specific immune responses in both mice models. A 100% protection rate was only obtained in the booster dose group of IFNα/β/γR−/− mice, indicating that this platform needs further optimization in future studies. In conclusion, we assessed a novel approach in CCHFV vaccination by introducing a conventional mRNA platform which can be considered in future experiments as an efficient and safe way to battle this disease.
Highlights
Crimean-Congo Hemorrhagic Fever (CCHF) is considered to be one of the main health concerns in endemic areas, from western China across southern Asia to the Middle East, Spain, and the Balkans, and throughout most of Africa [1].The causative agent belongs to the Bunyaviridae family, which includes a tripartite RNA genome of negative polarity [2]
We aimed to ascertain that small segment has potential to sufficiently elicit immune responses, especially, in the challenge assay; and secondly, we evaluated the efficacy of the conventional naked mRNA platform in battling against the Crimean-Congo Hemorrhagic Fever virus (CCHFV)
There are two main types of obstacles which researchers encounter in the field of CCHFV vaccine design
Summary
Crimean-Congo Hemorrhagic Fever (CCHF) is considered to be one of the main health concerns in endemic areas, from western China across southern Asia to the Middle East, Spain, and the Balkans, and throughout most of Africa [1]. Our group has obtained 100% protection rate in the challenged IFNα/β/γR−/− mice, using our newly developed Bovine herpesvirus 4-based viral vector that expresses the anti-nucleocapsid protein [8] In another recent study, a vesicular stomatitis virus-based vaccine delivering the CCHFV glycoprotein precursor (GPC) protected STAT-1 knock-out mice against CCHF [10]. To introduce a new expression platform in the struggle against this disease, we developed a conventional naked mRNA-based construct expressing the non-optimized S segment of the Ank-2 strain of CCHFV to evaluate its immunogenicity and protection against a challenge assay in two different mice models, namely C57BL/6 and IFNα/β/γR−/−. We aimed to ascertain that small segment has potential to sufficiently elicit immune responses, especially, in the challenge assay; and secondly, we evaluated the efficacy of the conventional naked mRNA platform in battling against the CCHFV
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