Development of Multi-epitope Based Subunit Vaccine Against Crimean-Congo Hemorrhagic Fever Virus Using Reverse Vaccinology Approach

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a viral disease caused by the Crimean-Congo hemorrhagic fever virus (CCHFV) of the Nairovirus genus. CCHF has occurred endemically in several regions of Africa, Southern Europe, and Central and Southeast Asia, with a case fatality rate of 5 to 80%. The World health organization enlisted CCHF as one of the top prioritized diseases for research and development in emergency contexts that making it a public health concern as no effective vaccine is available till date. Therefore, the present study aims to develop an effective multi-epitope subunit vaccine using immunoinformatics and reverse vaccinology approach against this virus. The B-cell and T-cell epitopes were predicted from structural and non-structural proteins, and filtered by immunogenicity, allergenicity, toxicity, conservancy, and cross-reactivity. The computational analysis revealed that the epitopes could induce an adequate immune response and had strong associations with their respective human leukocyte antigen (HLA) alleles with 98.94% of total world population coverage. Finally, the vaccine with 427 amino acids was constructed by connecting 8 cytotoxic T-lymphocytes, 4 helper T-lymphocytes, and 10 B-cell epitopes with appropriate linkers and β-defensin as an adjuvant. The antigenicity, allergenicity, solubility, and physiochemical properties of the vaccine were evaluated, followed by structural modelling, refinement, and validation. In addition, molecular docking and molecular dynamic simulations revealed a robust binding affinity and stability of the vaccine-immune receptor complex. Moreover, the codons were optimized for its higher expression in Escherichia coli ( E. coli ) K12 strain followed by in silico cloning. The proposed subunit vaccine developed in this study could be a potential candidate against CCHFV. However, further experimental validation is required to ensure the immunogenicity and safety profile of the proposed vaccine for combating and eradicating CCHFV. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-022-10430-0.

Evaluation of the immunogenicity of a Crimean-Congo hemorrhagic fever virus vaccine candidate in mice developed based on a baculovirus Zera nanoparticle delivery system

“…In recent years, with the rapid development of molecular biology as well as bioinformatics, researchers have developed various CCHF vaccine candidates ( 29 ), but there is no internationally recognized, safe and effective CCHF vaccine due to the lack of suitable animal models and secure biological laboratories needed to confirm their protective properties ( 30 ). Therefore, the development of a CCHF vaccine is an important topic.…”

In silico formulation of a next-generation multiepitope vaccine for use as a prophylactic candidate against Crimean-Congo hemorrhagic fever

“…To date, no specific anti-viral therapy or approved vaccine has been designed to treat or prevent infection that occurred through the virus. However, corticosteroid medications (dexamethasone and methylprednisolone), immunotherapy, neutralizing antibodies [ 9 ], and convalescent serum [ 10 ] are being considered as medication for CCHF. Among therapeutics, vaccines are proven to be most effective in combating infectious diseases, and rationally designed peptide vaccines have shown promising results in inducing a specific immune response.…”