Immunological Analysis of a CCHFV mRNA Vaccine Candidate in Mouse Models

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.

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

“…In an immunocompetent mice, NP based CCHFV vaccines developed with different platforms, uniformly induced IL-2, IL-10, IL-6, Il-4, TNF-α and IFN-γ [ 59 ]. In a CCHFV NP based mRNA vaccine study, IFN-γ an IL-4 levels were high in vaccinated mice before challenge [ 60 ]. The results from our study shows that rNP induced cytokines that could indicate balanced Th1/Th2 response.…”

Nucleoside-Modified mRNA Vaccines Protect IFNAR –/– Mice against Crimean-Congo Hemorrhagic Fever Virus Infection

“…Even though nucleoside-modified mRNA-LNP-based vaccine candidates have been used in vaccine studies against several infectious diseases ( 7 – 16 ), it has not been evaluated against CCHFV infection. However, naked mRNA, based on the S-segment of CCHFV (Ank-2 strain), has previously been used to immunize IFNAR −/− mice prior to CCHFV challenge ( 26 ), with a difference in success based on the immunization schedule.…”

The Integration of Human and Veterinary Studies for Better Understanding and Management of Crimean-Congo Haemorrhagic Fever

“…Studies investigating the immune response to this formalin inactivated vaccine have demonstrated that after four doses, low levels of neutralising antibodies are induced (112). Multiple other vaccine candidates for CCHFV have been developed using a wide range of platforms to deliver vaccine antigens (113)(114)(115)(116). For example, two doses of a protein-based subunit CCHFV vaccine that targeted Gn and Gc of the glycoprotein precursor achieved neutralising antibody responses, but did not confer protection in mouse challenge models (117).…”