Development of a broad-spectrum multiepitope vaccine against dabie bandavirus through immunoinformatic approaches

Abstract

Dabie bandavirus is an emerging tick-borne disease-causing high morbidity and mortality in East Asia, with no vaccines or targeted antiviral therapies. In this study, a multiepitope vaccine was designed using an immunoinformatic strategy to provide robust immune protection. The envelope polyprotein sequence was obtained from UniProt, and epitope prediction, conservancy screening, structural modeling, docking, immune simulations, codon optimization, and other computational analyses were performed. High antigenic, non-allergenic, and non-toxic T-cell epitopes were selected. The vaccine construct comprised 215 amino acids, exhibited an antigenicity score of 0.6922 and was predicted to be non-allergenic and non-toxic. Population coverage of selected T cell epitopes was found to be 89.76 % globally. The vaccine was calculated to be stable, soluble with a solubility score of 0.799, and thermally resistant. The predicted tertiary structure of the vaccine by Alphafold3 after refinement showed 97.7 % residues in the most favored region of the ramachandran plot. The molecular docking results of the vaccine with TLR4 showed the lowest energy of -1401.8 kcal/mol with the presence of 11 hydrogen bonds. Molecular dynamics simulations showed stable interactions between the vaccine and TLR4 receptor with an average RMSD of 4.5 Å and Rg of 30.0 Å. Free energy and PCA analysis confirmed thermodynamic stability and flexible yet stable interactions, supporting its immunogenic potential. Immune simulation analysis suggested durable responses from both B and T epitopes with increased cytokine production with IFN-γ and IL-2. In silico cloning into the pET28a(+) plasmid after codon optimization showed the possibility of expressing the vaccine, with GC content improving from 67.13 % to 54.42 %. However, further experimental validation is needed to check the safety and immune activation ability of the designed vaccine against Dabie bandavirus.

Keywords: B-cell epitopes; Dabie bandavirus; Immune simulations; Molecular docking molecular dynamic simulations; Multiepitope vaccine; T-cell epitopes.