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Modified mRNA Encoding the Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Confers Robust Protection
Sercan Keskin1,2, Shaikh Terkis Islam Pavel3,4, Rabia Sak1,5
1Department of Biotechnology, Institute of Health Sciences, Bezmialem Vakif University, Istanbul, Türkiye.
Journal of Medical Virology
|April 24, 2026
Summary
A new messenger ribonucleic acid (mRNA) vaccine candidate shows promise for Crimean-Congo Hemorrhagic Fever Virus (CCHFV). This nucleocapsid protein (NP)-based vaccine demonstrated 100% survival in mice challenged with CCHFV, offering a potential breakthrough for this high-priority pathogen.
Area of Science:
- Virology and Immunology
- Vaccine Development
- Molecular Biology
Background:
- Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a WHO priority pathogen with high mortality (up to 40%) and no approved vaccine.
- CCHFV's widespread endemicity, human-to-human transmission potential, and lack of treatment necessitate urgent vaccine development.
- Messenger ribonucleic acid (mRNA) vaccine technology has proven successful, as demonstrated during the COVID-19 pandemic.
Purpose of the Study:
- To develop and evaluate an mRNA vaccine candidate targeting the CCHFV nucleocapsid protein (NP).
- To assess the preclinical efficacy of a pseudouridine-modified mRNA vaccine encoding CCHFV NP in mouse models.
Main Methods:
- Designed and synthesized pseudouridine-modified mRNA (IVT NP-ΨmRNA) encoding CCHFV NP.
- Confirmed biochemical and immunological properties of NP in vitro.
- Evaluated vaccine efficacy in immunocompetent BALB/c and immunosuppressed (IS) C57BL/6 mice, including challenge studies with lethal CCHFV doses.
- Administered two doses of naked or PLGA-encapsulated IVT NP-ΨmRNA or unmodified mRNA 14 days apart.
Main Results:
- Immunization with IVT NP-ΨmRNA induced robust CCHFV NP-specific humoral (IgM, IgG) and cellular (cytokine, lymphoproliferative) responses in BALB/c mice.
- Both naked and PLGA-encapsulated IVT NP-ΨmRNA achieved 100% survival in IS C57BL/6 mice following lethal CCHFV challenge.
- Unmodified IVT NP-mRNA vaccination resulted in only 20% survival, while inactivated CCHFV vaccine showed 100% survival.
- Viral clearance was observed in spleen, liver, and blood of protected mice by day 14 post-challenge.
Conclusions:
- Pseudouridine-modified mRNA encoding CCHFV NP provides significant survival benefits in a lethal CCHFV mouse model.
- The NP protein is a viable target for CCHFV vaccine development, demonstrating protective immunity.
- This study provides a strong foundation for further preclinical development of NP-based mRNA vaccines against CCHFV.
