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.
Highlights
Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Orthonairovirus genus and Nairoviridae family, causes a hemorrhagic fever disease with considerable mortality rates in endemic areas such as Turkey [1,2]
The created recombinant BoHV4-∆TK-CCHFV-N showed a similar pattern of cytopathic effects (CPEs) in the MDBK cells compared to its respective virus (Movar33/63; Figure 1E,F)
In addition to employing inactivated viruses, various strategies have been explored for an effective CCHFV vaccine development such as targeting viral glycoproteins and the nucleocapsid using several DNA or virus-like particle-based vaccines [6,27,28]
Summary
Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Orthonairovirus genus and Nairoviridae family, causes a hemorrhagic fever disease with considerable mortality rates in endemic areas such as Turkey [1,2]. The CCHFV nucleocapsid (N) protein is an important structural component with the potential to stimulate humoral and cellular responses following natural or experimental infections It has, been targeted for vaccine development using DNA and viral vector platforms in several studies [5,6,7]. During challenge experiments in different modified mice models, such as IFNα/β/γR−/−, immune-suppressed (IS) and STAT-1 knock-out mice, vaccinations based on this protein have demonstrated protective effects in lethal challenges despite the lack of neutralizing antibodies [6,8]. Different expression platforms such as adenovirus and modified vaccinia Ankara (MVA)-based vectors were previously used to deliver N proteins with inconclusive results.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
