In silico design and analyses of a multi-epitope vaccine against Crimean-Congo hemorrhagic fever virus through reverse vaccinology and immunoinformatics approaches

Abstract

Crimean Congo Hemorrhagic Fever virus (CCHFV) is a deadly human pathogen that causes an emerging zoonotic disease with a broad geographic spread, especially in Africa, Asia, and Europe, and the second most common viral hemorrhagic fever and widely transmitted tick-borne viral disease. Following infection, the patients are presented with a variety of clinical manifestations and a fatality rate of 40%. Despite the high fatality rate, there are unmet clinical interventions, as no antiviral drugs or vaccines for CCHF have been approved. Immunoinformatics pipeline and reverse vaccinology were used in this study to design a multi-epitope vaccine that may elicit a protective humoral and cellular immune response against Crimean-Congo hemorrhagic fever virus infection. Three essential virulent and antigenic proteins (S, M, and L) were used to predict seven CTL and 18 HTL epitopes that were non-allergenic, antigenic, IFN-γ inducing, and non-toxic. The epitopes were connected using linkers and 50S ribosomal protein L7/L12 was used as an adjuvant and raised a multi-epitope vaccine (MEV) that is 567 amino acids long. Molecular docking and simulation of the predicted 3D structure of the MEV with the toll-like (TLR2, TLR3, and TLR4) receptors and major histocompatibility complex (MCH-I and MCH-II) indicate high interactions and stability of the complexes, MM-GBSA free binding energy calculation revealed a favourable protein–protein complex. Maximum MEV expression was achieved with a CAI value of 0.98 through in silico cloning in the Drosophila melanogaster host. According to the immune simulation, IgG1, T-helper cells, T-cytotoxic cells, INF-γ, and IL-2 were predicted to be significantly elevated. These robust computational analyses demonstrated that the proposed MEV is effective in preventing CCHFV infections. However, it is still necessary to conduct both in vitro and in vivo experiments to validate the potential of the vaccine.

Development of membrane protein‐based vaccine against lumpy skin disease virus (LSDV) using immunoinformatic tools

“…The aliphatic index and low GRAVY score indicate the thermostable and hydrophilic nature of the vaccine candidate (Abdi et al., 2022 ; Susithra Priyadarshni et al., 2022 ; Validi et al., 2018 ). Moreover, the GRAVY value 0.008 of the vaccine suggesting that the vaccine may interact with water (Abdi et al., 2022 ), and this vaccine is ideal for its usage in endemic areas (Bachmann & Jennings, 2010 ; Omoniyi et al., 2022 ). The secondary structure analysis of the vaccine construct indicated that the alpha‐helices dominating the structure followed by random coil and beta sheets, which are suggestive of the existence of natively unfolded protein regions that can be identified by antibodies, produced in response to infection (Bibi et al., 2021 ).…”

“…Codon optimization was carried out in D. melanogaster to ensure that the vaccination protein was fully expressed (Akmammedov et al., 2017 ; Gori et al., 2013 ). Codon optimization was done for the D. melanogaster strain; the estimated GC content and CAI indicated enhanced transcriptional and translational efficiency (Omoniyi et al., 2022 ). A D. melanogaster ‐based expression system selected because it enables recombinant protein production on a large scale at a low cost (Omoniyi et al., 2022 ).…”

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

“…Mainly four TLRs (TLR-3,4,7, and 8) broadly act as viral antigenic receptors and play a crucial role against viral infections [ 102 ] whereas TLR-1,2,5,6,9–12 primarily work against bacterial infection [ 102 ]. TLR3, which senses viral dsRNA and structured RNA, is associated with acute CCHF, and enhances the activity of the protein, can stimulate innate immune responses [ 103 – 106 ]. Therefore, the activity of these receptors with the desired vaccine candidate has been observed in this study.…”

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant

“…Another observation of interest was that the level of IFN-γ was elevated following the first injection and remained at the peaks after repeated the injections. This shows a high concentration of T helper cells and thus the efficient production of immunoglobulin, which supports humoral responses [ 119 ]. To enhance the expression of the designed vaccine in E. coli K-12, codon adaptation was conducted through JCat tool.…”

“…In numerous recent studies, the reliable computational procedures have been used to select efficient epitopes and design novel vaccines against various pathogens such as Mycobacterium tuberculosis [ 118 ], Helicobacter Pylori [ 42 ], Onchocerca volvulus [ 111 ], Plasmodium [ 120 ], and Crimean-Congo hemorrhagic fever virus [ 119 ]. In this respect, the present study recommends a final peptide construct as the best epitope vaccine based on the strategies used in the research to be an attractive intervention against the Streptococcus pneumoniae pathogen.…”