Assessment of the Immunogenicity and Protective Aspects of a DNA Vaccine Targeting Crimean Congo Hemorrhagic Fever Virus Glycoprotein Gc

Abstract

Aim: Crimean Congo Hemorrhagic Fever (CCHF) is a lethal, endemic infectious disease in human. For the preventive measures of the disease, there is currently no safe and efficient vaccine, widely for human use. Vaccine development for CCHF virus is an actively researched subject. In this study, we aimed to investigate the immunizing and protective potentials of the CCHF virus surface glycoprotein Gc that is delivered as a single antigen via a DNA based vaccine vector. Material and Methods: A DNA based vaccine targeting the immunogenic envelope glycoprotein Gc of a CCHF virus isolate with Turkey origin (Ank2) was generated and its immunogenicity and protective capability against lethal challenge in IFNα/βR-/- receptor knock out mice was assessed. Results: The developed vaccine candidate (pGc) elicited a considerable amount of neutralizing antibody responses in the vaccinated mice. The vaccine candidate significantly induced both antiviral Th1 and B cell activating Th2 immune responses deduced from the cytokine production profiles in the vaccinated mice. However, despite the immune responses elicited post-immunization, the vaccine failed to confer protection against lethal CCHF virus infection. Conclusion: To the best of our knowledge, this is the first report of a DNA vaccine candidate generated against CCHF virus based on the glycoprotein Gc. The pGc vaccine candidate exhibited antigen-specific immunity in IFN/α/βR-/- mice, but was unable to produce a protection upon lethal challenge with the homologous CCHF virus. Once we comprehensively understand the immune correlates of protection, we will be more eligible to significantly improve the efficacy of vaccines.

Keywords

• crimean congo hemorrhagic fever virus
• dna vaccine
• immune responses
• lethal challenge
• kırım kongo kanamalı ateşi virüsü
• dna aşısı
• i̇mmün yanıt
• ölümcül sınama