Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Adjuvant Potential of CD24 on Immunogenicity and Lethal Challenge Protection of a DNA vector Expressing Nucleocapsid Protein of Crimean Congo Hemorrhagic Fever Virus

Version 1 : Received: 26 November 2018 / Approved: 27 November 2018 / Online: 27 November 2018 (12:15:59 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

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. Imminent public health threat posed by 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 nucleocapsid protein (N) of CCHFV (pV-N13) and investigated its potential to stimulate cytokine and total/specific antibody responses in BALB/c and challenge experiment in IFNAR-/- mice. Due to lack of sufficient antibody stimulation towards N protein, we have selected CD24 protein as a potential adjuvant which has proliferative effect on B and T cells. Overall, our N expressing construct when administered solely or in combination with pCD24 vector elicited significant cellular and humoral responses in BALB/c, despite variations in particular cytokines and total antibodies. However, the stimulated antibodies produced due to expression of N protein have shown no neutralizing ability in VNA. Furthermore, challenge experiments were revealed protection potential of N expressing construct in IFNAR -/- mice model. In conclusion, we have shown that CD24 has prominent effect as a genetic adjuvant when co-delivers with a synergic foreign gene expressing vector. Besides, targeting of S segment of CCHFV can be considered as a practical way in developing vaccine against this virus due to its ability to induce immune response which leads to protection in challenge assays in IFN-gamma defective mice models.

Keywords

CCHFV, CD24, nucleocapsid, genetic adjuvant, immunogenicity, IFNAR-/- mice

Subject

Biology and Life Sciences, Virology

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