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Bovine Herpesvirus Type 4 (BoHV-4) Vector Delivering Nucleocapsid Protein of Crimean-Congo Hemorrhagic Fever Virus Induces Comparable Protective Immunity against Lethal Challenge in IFNα/β/γR−/− Mice Models

1
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey
2
Biotechnology Institute, Ankara University, Ankara 06560, Turkey
3
Virology Unit, Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey
4
Infectious Diseases Clinic, Saglik Bilimleri University, Numune Training and Research Hospital, Ankara 06100, Turkey
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 237; https://doi.org/10.3390/v11030237
Received: 29 January 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 9 March 2019
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with a significant mortality rate of up to 40% in endemic areas, with evidence of geographical expansion. Due to a lack of effective therapeutics and control measures, the development of a protective CCHFV vaccine remains a crucial public health task. This paper describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4)-based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity in BALB/c and protection potential in IFNα/β/γR−/− mice models in comparison with two routinely used vaccine platforms, namely, Adenovirus type 5 and a DNA vector (pCDNA3.1 myc/His A), expressing the same antigen. All vaccine constructs successfully elicited significantly elevated cytokine levels and specific antibody responses in immunized BALB/c and IFNα/β/γR−/− mice. However, despite highly specific antibody responses in both animal models, the antibodies produced were unable to neutralize the virus in vitro. In the challenge experiment, only the BoHV4-∆TK-CCHFV-N and Ad5-N constructs produced 100% protection against lethal doses of the CCHFV Ank-2 strain in IFNα/β/γR−/− mice. The delivery platforms could not be compared due to similar protection rates in IFNα/β/γR−/− mice. However, during the challenge experiment in the T cell and passive antibody transfer assay, BoHV4-∆TK-CCHFV-N was dominant, with a protection rate of 75% compared to others. In conclusion, vector-based CCHFV N protein expression constitutes an effective approach for vaccine development and BoHV-4 emerged as a strong alternative to previously used viral vectors. View Full-Text
Keywords: Crimean-Congo hemorrhagic fever; nucleocapsid; bovine herpesvirus type 4; IFNα/β/γR−/− mice; lethal dose; passive antibody transfer Crimean-Congo hemorrhagic fever; nucleocapsid; bovine herpesvirus type 4; IFNα/β/γR−/− mice; lethal dose; passive antibody transfer
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Aligholipour Farzani, T.; Földes, K.; Hanifehnezhad, A.; Yener Ilce, B.; Bilge Dagalp, S.; Amirzadeh Khiabani, N.; Ergünay, K.; Alkan, F.; Karaoglu, T.; Bodur, H.; Ozkul, A. Bovine Herpesvirus Type 4 (BoHV-4) Vector Delivering Nucleocapsid Protein of Crimean-Congo Hemorrhagic Fever Virus Induces Comparable Protective Immunity against Lethal Challenge in IFNα/β/γR−/− Mice Models. Viruses 2019, 11, 237.

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