Akademik Veri Yönetim Sistemi
Tez Türü: Doktora
Tezin Yürütüldüğü Kurum: Erciyes Üniversitesi, Sağlık Bilimleri Enstitüsü, --, Türkiye
Tez Danışmanı: Aykut Özdarendeli
Tezin Onay Tarihi: 2023
Tezin Dili: İngilizce
Özet:
Crimean-Congo hemorrhagic fever virus (CCHFV), belonging to the Nairoviridae family and Bunyavirales order, is primarily transmitted to humans through tick bites or contact with the blood of infected animals. This virus can lead to severe symptoms, such as hemorrhagic fever, and has a mortality rate ranging from 5 to 30%. Given its high fatality rate and the lack of effective medical countermeasures, CCHFV is classified as a high-priority pathogen by the who (WHO). Currently, Türkiye is experiencing an exceptional outbreak of Crimean Congo Hemorrhagic Fever (CCHF), with more than 10,000 reported cases. At present, there are no globally licensed antivirals or vaccines available for CCHFV. The aim of this thesis is to develop Adenovirus (Ad)-based recombinant vaccines by using a novel antigen design technique termed Bioinformatically Generated Conserved Antigen (BGCA) against CCHF. We have constructed to recombinant Ad-BGCA CCHFV nucleoprotein (NP) V and Ad-BGCA CCHFV glycoprotein (GPC) V that represent the Balkans, Russia, Georgia as well as our country and developed Ad-BGCA CCHFV NP I-VI construct representing all genotypes of the CCHFV. The findings presented in this thesis provide compelling evidence regarding the immunogenicity and protective efficacy of the Ad vector-based recombinant vaccine candidates, particularly the Ad-BGCA CCHFV GPC V + Ad-BGCA CCHFV NP I-VI vaccine candidate, against CCHFV. Immunized animals exhibited a robust immune response, characterized by high levels of CCHFV-specific antibodies and T-cell responses. Importantly, the Ad-BGCA CCHFV GPC V + Ad-BGCA CCHFV NP I-VI vaccine candidate demonstrated complete protection, achieving a 100% success rate, against lethal CCHFV challenges in a transgenic animal model. These highly promising results underscore the necessity for further investigation through clinical studies, aiming to advance the development of this vaccine candidate for potential use in preventing CCHFV infections in humans.