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Viruses. 2019 Mar 9;11(3). pii: E237. doi: 10.3390/v11030237.

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.

Author information

1
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. touraj.farzani@gmail.com.
2
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. fldeskatalin@gmail.com.
3
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. alireza.hanifehnezhad@gmail.com.
4
Biotechnology Institute, Ankara University, Ankara 06560, Turkey. byener@ankara.edu.tr.
5
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. sevalbilge@hotmail.com.
6
Biotechnology Institute, Ankara University, Ankara 06560, Turkey. Neda.Khiabani@hotmail.com.
7
Virology Unit, Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey. ekoray@hacettepe.edu.tr.
8
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. alkanferay@gmail.com.
9
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. tanerkaraoglu@gmail.com.
10
Infectious Diseases Clinic, Saglik Bilimleri University, Numune Training and Research Hospital, Ankara 06100, Turkey. hurrembodur@gmail.com.
11
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey. ozkul@ankara.edu.tr.
12
Biotechnology Institute, Ankara University, Ankara 06560, Turkey. ozkul@ankara.edu.tr.

Abstract

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.

KEYWORDS:

Crimean-Congo hemorrhagic fever; IFNα/β/γR−/− mice; bovine herpesvirus type 4; lethal dose; nucleocapsid; passive antibody transfer

PMID:
30857305
PMCID:
PMC6466008
DOI:
10.3390/v11030237
[Indexed for MEDLINE]
Free PMC Article

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