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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 IFN alpha/beta/gamma R-/- Mice Models

2019    Farzani, Touraj Aligholipour; Foldes, Katalin; Hanifehnezhad, Alireza; Ilce, Burcu Yener; Dagalp, Seval Bilge; Khiabani, Neda Amirzadeh; Erguenay, Koray; Alkan, Feray; Karaoglu, Taner; Bodur, Hurrem; Ozkul, Aykut

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- increment TK-CCHFV-N) and its immunogenicity in BALB/c and protection potential in IFN alpha/beta/gamma R-/- 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 IFN alpha/beta/gamma R-/- 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- increment TK-CCHFV-N and Ad5-N constructs produced 100% protection against lethal doses of the CCHFV Ank-2 strain in IFN alpha/beta/gamma R-/- mice. The delivery platforms could not be compared due to similar protection rates in IFN alpha/beta/gamma R-/- mice. However, during the challenge experiment in the T cell and passive antibody transfer assay, BoHV4- increment 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.