{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:00:59Z","timestamp":1791381659758,"version":"4.3.3"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The Crimean\u2010Congo Hemorrhagic Fever Virus (\n                    <jats:italic>Orthonairovirus haemorrhagiae<\/jats:italic>\n                    ) causes a hemorrhagic fever with mortality rates reaching up to 40%. For years, this virus has maintained its position among the top priority pathogens identified by the World Health Organization (WHO). This is due to its endemic presence across a vast region\u2014from Africa and Spain to the Balkans, the Middle East, and throughout Asia\u2014its potential for human\u2010to\u2010human transmission, and the lack of an effective and approved vaccine or treatment. Therefore, the development of an effective vaccine against CCHFV is of critical importance. Building on the success of mRNA\u2010based vaccines during the Coronavirus Disease 2019 (COVID\u201019) pandemic, this study reports the development of a messenger ribonucleic acid (mRNA) vaccine candidate expressing the nucleocapsid protein (NP) of CCHFV. The CCHFV NP in vitro transcript (IVT) was designed with pseudouridine (\u03a8) nucleoside modification. As part of the preclinical characterization of the IVT vaccine candidate, the biochemical and immunological properties of NP were confirmed in Huh\u20107 cells transfected with IVT NP\u2010\u03a8mRNA. Afterwards, the efficacy of IVT NP\u2010\u03a8mRNA immunization was evaluated in immunocompetent BALB\/c and transiently immunosuppressed (IS) C57BL\/6 mice. In CCHFV challenge studies, IS C57BL\/6 mice were used. IS C57BL\/6 mice were immunized intramuscularly with 2 doses of IVT NP\u2010 \u03a8mRNA, either naked or encapsulated in Poly(lactic\u2010co\u2010glycolic acid) (PLGA) nanoparticles, administered 14 days apart. High levels of CCHFV NP\u2010specific humoral (IgM and IgG) and cellular (cytokine and lymphoproliferative) responses were demonstrated in BALB\/c mice immunized with IVT NP\u2010 \u03a8mRNA. In challenge experiments, 100% survival was observed with both the naked and PLGA\u2010encapsulated IVT NP\u2010\u03a8mRNA immunizations. These findings demonstrate 100% survival following lethal CCHFV challenge under the experimental conditions tested in this mouse model and support the potential of NP\u2010encoding pseudouridine\u2010modified mRNA vaccines. Additionally, 100% survival was observed in mice immunized with inactivated CCHFV, whereas only 20% survival was detected in the unmodified IVT NP\u2010mRNA vaccinated animals. In the protected mice, viral clearance was observed in the spleen, liver tissues, and blood on day 14 post\u2010challenge. This study demonstrates that NP, the most abundant protein of the virus, is capable of providing significant survival benefits in the tested mouse model. Furthermore, our report represents a significant step in identifying a potential vaccine candidate and provides a solid foundation for further preclinical studies necessary to support future clinical development.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70940","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T10:08:26Z","timestamp":1777025306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modified mRNA Encoding the Crimean\u2010Congo Hemorrhagic Fever Virus Nucleocapsid Protein Confers Robust Protection Against Lethal Challenge in Mice"],"prefix":"10.1002","volume":"98","author":[{"given":"Sercan","family":"Keskin","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Institute of Health Sciences Bezmialem Vakif University Istanbul T\u00fcrkiye"},{"name":"Department of Microbiology, Beykoz Institute of Life Sciences and Biotechnology Bezmialem Vakif University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-0943","authenticated-orcid":false,"given":"Shaikh Terkis Islam","family":"Pavel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Erciyes University Kayseri T\u00fcrkiye"},{"name":"Vaccine Research, Development and Application Centre (ERAGEM) Erciyes University Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia","family":"Sak","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Health Sciences Bezmialem Vakif University Istanbul T\u00fcrkiye"},{"name":"Department of Pharmaceutical Biotechnology, Faculty of Pharmacy Bezmialem Vakif University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Bahadori","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy Cerrahpa\u015fa University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Furkan","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Erciyes University Kayseri T\u00fcrkiye"},{"name":"Vaccine Research, Development and Application Centre (ERAGEM) Erciyes University Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcnir","family":"Akta\u015f","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine University of Firat Elazig T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruk","family":"Karake\u00e7ili","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine Erzincan Binali Yildirim University Erzincan T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Kalkan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Medical Faculty Karadeniz Technical University Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aykut","family":"\u00d6zdarendeli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Erciyes University Kayseri T\u00fcrkiye"},{"name":"Vaccine Research, Development and Application Centre (ERAGEM) Erciyes University Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2066-0252","authenticated-orcid":false,"given":"Mehmet Ziya","family":"Doymaz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Beykoz Institute of Life Sciences and Biotechnology Bezmialem Vakif University Istanbul T\u00fcrkiye"},{"name":"Department of Medical Microbiology, Medical School Bezmialem Vakif University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_27_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.07.006"},{"key":"e_1_2_27_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-016-3162-7"},{"key":"e_1_2_27_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01672-3"},{"key":"e_1_2_27_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00871-9"},{"key":"e_1_2_27_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2020.101403"},{"key":"e_1_2_27_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615162"},{"key":"e_1_2_27_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2020.101429"},{"key":"e_1_2_27_9_1","unstructured":"WHO. 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