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Viruses 2019, 11(1), 75; https://doi.org/10.3390/v11010075

Co-Delivery Effect of CD24 on the Immunogenicity and Lethal Challenge Protection of a DNA Vector Expressing Nucleocapsid Protein of Crimean Congo Hemorrhagic Fever Virus

1
Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey
2
Virology Unit, Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey
3
Biotechnology Institute, Ankara University, Ankara 06560, Turkey
*
Author to whom correspondence should be addressed.
Received: 26 November 2018 / Revised: 10 January 2019 / Accepted: 12 January 2019 / Published: 17 January 2019
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Abstract

Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection, with an eminent risk of fatal human disease. The imminent public health threat posed by the disseminated virus activity and lack of an approved therapeutic make CCHFV an urgent target for vaccine development. We described the construction of a DNA vector expressing a nucleocapsid protein (N) of CCHFV (pV-N13), and investigated its potential to stimulate the cytokine and total/specific antibody responses in BALB/c and a challenge experiment in IFNAR−/− mice. Because of a lack of sufficient antibody stimulation towards the N protein, we have selected cluster of differentiation 24 (CD24) protein as a potential adjuvant, which has a proliferative effect on B and T cells. Overall, our N expressing construct, when administered solely or in combination with the pCD24 vector, elicited significant cellular and humoral responses in BALB/c, despite variations in the particular cytokines and total antibodies. However, the stimulated antibodies produced as a result of the N protein expression have shown no neutralizing ability in the virus neutralization assay. Furthermore, the challenge experiments revealed the protection potential of the N expressing construct in an IFNAR −/− mice model. The cytokine analysis in the IFNAR−/− mice showed an elevation in the IL-6 and TNF-alpha levels. In conclusion, we have shown that targeting the S segment of CCHFV can be considered for a practical way to develop a vaccine against this virus, because of its ability to induce an immune response, which leads to protection in the challenge assays in the interferon (IFN)-gamma defective mice models. Moreover, CD24 has a prominent immunologic effect when it co-delivers with a suitable foreign gene expressing vector. View Full-Text
Keywords: CCHFV; CD24; Cytokines; nucleocapsid; IFNAR−/− mice; Lethal Challenge CCHFV; CD24; Cytokines; nucleocapsid; IFNAR−/− mice; Lethal Challenge
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Aligholipour Farzani, T.; Hanifehnezhad, A.; Földes, K.; Ergünay, K.; Yilmaz, E.; Hashim Mohamed Ali, H.; Ozkul, A. Co-Delivery Effect of CD24 on the Immunogenicity and Lethal Challenge Protection of a DNA Vector Expressing Nucleocapsid Protein of Crimean Congo Hemorrhagic Fever Virus. Viruses 2019, 11, 75.

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