In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches

Int J Biol Macromol. 2024 May;267(Pt 2):131517. doi: 10.1016/j.ijbiomac.2024.131517. Epub 2024 Apr 15.

Abstract

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful.

Keywords: Bioinformatics; HCV; Multi-epitope vaccine.

MeSH terms

  • Computational Biology* / methods
  • Computer Simulation
  • Epitopes, B-Lymphocyte* / chemistry
  • Epitopes, B-Lymphocyte* / immunology
  • Epitopes, T-Lymphocyte* / chemistry
  • Epitopes, T-Lymphocyte* / immunology
  • Hepacivirus* / immunology
  • Hepatitis C* / immunology
  • Hepatitis C* / prevention & control
  • Humans
  • Immunoinformatics
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Toll-Like Receptor 2 / chemistry
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / immunology
  • Viral Hepatitis Vaccines / chemistry
  • Viral Hepatitis Vaccines / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Epitopes, B-Lymphocyte
  • Toll-Like Receptor 4
  • Toll-Like Receptor 2
  • Viral Hepatitis Vaccines
  • Viral Envelope Proteins