Design and validation of a novel multi-epitopes vaccine against hantavirus

J Biomol Struct Dyn. 2024 May;42(8):4185-4195. doi: 10.1080/07391102.2023.2219324. Epub 2023 Jun 1.

Abstract

Hantavirus is a member of the order Bunyavirales and an emerging global pathogen. Hantavirus infections have affected millions of people globally based on available epidemiological data and research studies. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are the two main human diseases associated with hantavirus infections. Hence, efforts are required to develop a potent vaccine against the pathogen. The only vaccine that is in use for hantavirus is an inactivated virus vaccine, "Hantavax", but it failed to produce neutralizing antibodies. Vaccine development is of much importance in dealing with the surge of hantavirus globally. In this study, hantavirus five proteins (N protein, G1 and G2, L protein, and non-structural proteins) were used in NetCTL 1.2 program to predict T-cell epitopes. To predict major histocompatibility complex (MHC) binding alleles, an immune epitope database (IEDB) was used. All predicted epitopes were then investigated for different immunoinformatics analyses such as antigenicity and toxicity analyses. The good water-soluble, non-toxic, probable antigenic, and DRB*0101 binder was selected. A multi-epitopes-based vaccine designing was then done where linkers were used to connect the shortlisted epitopes. In addition, an adjuvant molecule was supplementary to the multi-epitopes peptide to improve the vaccine's immunogenic potential. The final vaccine construct's three-dimensional structure was modeled by ab initio method. The vaccine molecule was then evaluated for its binding potential with TLR-3 immune receptor, which is key for its recognition and processing by the host immune system. Docking studies were performed using HADDOCK software. The best-docked complex was selected and visualized for intermolecular binding and interactions using UCSF Chimera 1.16 software. The findings revealed that the designed vaccine might be a potential vaccine against hantavirus and can be used in experimental animal model testings.Communicated by Ramaswamy H. Sarma.

Keywords: Hantavirus; docking analysis; immunoinformatic; molecular docking; multi-epitopes-based vaccine.

MeSH terms

  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes, T-Lymphocyte* / chemistry
  • Epitopes, T-Lymphocyte* / immunology
  • Hantavirus Infections / immunology
  • Hantavirus Infections / prevention & control
  • Humans
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation
  • Orthohantavirus* / chemistry
  • Orthohantavirus* / immunology
  • Protein Binding
  • Viral Vaccines* / chemistry
  • Viral Vaccines* / immunology

Substances

  • Viral Vaccines
  • Epitopes, T-Lymphocyte
  • Epitopes