Designing a novel multi‑epitope vaccine against Ebola virus using reverse vaccinology approach

Abstract

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

Insight into the first multi-epitope-based peptide subunit vaccine against avian influenza A virus (H5N6): An immunoinformatics approach

“…Disulfide engineering is a novel method of creating new disulfide bonds in a protein of interest by changing cysteine residues in the protein structure, leading to increased protein structure stability ( Mugunthan and Harish, 2021 ). As a result, the Disulfide by Design 2 (DbD2) server ( http://cptweb.cpt.wayne.edu/DbD2/ ) was used to identify residue pairs with the potential for mutation and could be used in disulfide engineering ( Alizadeh et al, 2022 ) ( Fig. 9 ).…”

Integration: Gospel for immune bioinformatician on epitope-based therapy

“…For example, considering the risk of Ebola virus and the harsh nature of the required test conditions, Alizadeh et al. resigned the evaluation after designing a multiepitope vaccine against Ebola virus ( 35 ). However, we found a connection between different types of epitope analysis, so the results of multiple analyses can be compared to validate the results at the bioinformatics level.…”

In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis

“…Adjuvants are important components of vaccines that can boost innate and adaptive immune responses [99] . Many proteins from M. tuberculosis have adjuvant properties and have been used to design vaccine [17] , [27] , [87] , [100] , [101] , [102] , [103] , [104] , [105] . One of the most widely used is HBHA [100] , [101] , [102] , [103] , [104] , [105] , which is a potent immunostimulant that induces dendritic cells (DCs) maturation through TLR4 processing [105] , [106] .…”

“…Multi-epitope vaccine, a recombinant protein consisting of a series of or overlapping epitopes (peptides) [16] , is a novel type of vaccine candidate that may address the above issues. In recent years, multi-epitope vaccines have attracted much attention due to their advantages of higher immunity and lower allergenicity than conventional vaccines [17] , [18] . Currently, multi-epitope vaccines have been designed against many pathogenic microorganisms, including Shigella spp.…”