Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 29 January 2019 / Approved: 31 January 2019 / Online: 31 January 2019 (05:26:35 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Viruses 2019, 11, 237
DOI: 10.3390/v11030237

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with significant mortality rate of up to 40% in the endemic areas, with evidence for geographical expansion. Lacking effective therapeutics and control measures, the development of protective CCHFV vaccine remains a crucial public health task. This manuscript describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4) based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity and protection potential in BALB/c and IFNAR-/- mice models in comparison with Adenovirus type 5 (Ad5-N) and pCDNA3.1 myc/His A (pCD-N1), two widely used vaccine platforms. All constructs expressing viral nucleocapsid (N) protein successfully elicited cytokine and total/specific antibody responses in BALB/c mice. BoHV4-∆TK-CCHFV-N and Ad5-N constructs further produced 100% protection in IFNAR-/- mice during CCHFV Ank-2 strain lethal challenge. Despite elevated specific antibody responses in both animal models, the produced antibodies were unable to neutralize the virus in vitro. A comparison of delivery platforms was not possible, due to similar protection rates in IFNAR-/- mice. In conclusion, vector-based CCHFV N protein expression proved to constitute an effective approach for the vaccine development pipeline and BoHV-4 emerged as a strong alternative to previously-used virus vectors.

Subject Areas

Crimean-Congo hemorrhagic fever; nucleocapsid; Bovine herpesvirus type 4; IFNAR-/- mice; lethal dose

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