Design of a novel multi-epitope vaccine candidate against hepatitis C virus using structural and nonstructural proteins: An immunoinformatics approach

Abstract

Hepatitis C virus (HCV) infects the liver and causes chronic infection. Several mutations in the viral genome have been associated with drug resistance development. Currently, there is no approved vaccine against the HCV. The employment of computational biology is the primary and crucial step for vaccine design or antiviral therapy which can substantially reduce the duration and cost of studies. Therefore, in this study, we designed a multi-epitope vaccine using various immunoinformatics tools to elicit the efficient human immune responses against the HCV. Initially, various potential (antigenic, immunogenic, non-toxic and non-allergenic) epitope segments were extracted from viral structural and non-structural protein sequences using multiple screening methods. The selected epitopes were linked to each other properly. Then, toll-like receptors (TLRs) 3 and 4 agonists (50S ribosomal protein L7/L12 and human β-defensin 2, respectively) were added to the N-terminus of the final vaccine sequence to increase its immunogenicity. The 3D structure of the vaccine was modeled. Molecular dynamics simulations studies verified the high stability of final free vaccines and in complex with TLR3 and TLR4. These constructs were also antigenic, non-allergenic, nontoxic and immunogenic. Although the designed vaccine traits were promising as a potential candidate against the HCV infection, experimental studies and clinical trials are required to verify the protective traits and safety of the designed vaccine.

Designing a Novel Multiepitope Vaccine from the Human Papilloma Virus E1 and E2 Proteins for Indonesia with Immunoinformatics and Molecular Dynamics Approaches

“…The reverse vaccinology is a promising method for vaccine development. Previous research have resulted in the development of vaccines through the process of reverse vaccinology, which involves the production of vaccine against Jamestown canyon virus, 49 hepatitis C virus, 50 monkeypox virus, 51 chikungunya virus, 52 Burkholderia pseudomallei, 53 and lumpy skin disease. 54 The immunoinformatics prediction results have also been tested for validity both in vivo and in vitro.…”

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

“…The in silico validations like molecular docking and in silico cloning and immune simulation were included in this study to design and develop multi-epitope vaccine construct against LSDV infection (Ashfaq et al, 2021;Behbahani et al, 2021;Hossain et al, 2021;Sanches et al, 2021). The purpose of multi-epitope vaccine is to enhance the humoral and cell-mediated immune response by identifying the specific MHC I, MHC II and B-cell epitopes from the antigenic proteins.…”

“…Immunoinformatics and computational vaccinology become an invaluable tool for more rapid and precise vaccine design (Ishack & Lipner, 2021 ). The design of a multi‐epitope vaccine targeting viral structural and non‐structural proteins through immunoinformatics tools appears promising (Behmard et al., 2022 ; Fadaka et al., 2021 ; Huang et al., 2022 ). However, there is very limited information on immunoinformatics approaches to develop LSD vaccine.…”

TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview

“…Notably, DAA therapy has been associated with an increasing risk of hepatocellular carcinoma (HCC) in patients treated with DAAs ( Chinchilla-Lopez et al, 2017 ; Tajiri et al, 2022 ). Currently, there is no licensed protective vaccine against HCV, making the development of an effective preventive vaccine is critical ( Behmard et al, 2022 ).…”

“…Scientists are diligently working on different strategies to develop an effective HCV vaccine. Immunoinformatics-based multi-epitope constructs, along with the use of TLR3 and TLR4 agonists, have shown immunogenicity, non-allergenicity, and non-toxicity ( Behmard et al, 2022 ), requiring further investigation into the protective traits and safety of these designed candidates. The improved efficacy of HCV vaccine candidates due to TLR agonists has been reported in several studies.…”