Immunoinformatics-driven design of a multi-epitope vaccine against Seoul Virus: Structural, dynamic, and immunogenic...

Seoul Virus (SEOV), a zoonotic hantavirus, is a major cause of Hemorrhagic Fever with Renal Syndrome (HFRS) and represents a global health challenge. With no licensed vaccines or specific antivirals available, this study aimed to design a glycoprotein-based multi-epitope vaccine against SEOV using immunoinformatics approaches.

MHC-I and MHC-II epitopes were predicted via the Immune Epitope Database (IEDB) and screened for antigenicity, non-allergenicity, and non-toxicity. Four constructs were designed, with V2 selected as the best candidate. Structural modeling was performed using AlphaFold3 and validated with Ramachandran analysis. Molecular docking with Toll-like receptor-4, molecular dynamics simulations, and immune simulations were conducted to evaluate stability and immunogenicity.

The V2 construct demonstrated high antigenicity (0.683) and broad population coverage (95.94%). Structural validation confirmed 95.6% of residues in favored regions. Docking revealed strong binding to Toll-like receptor-4, and dynamics confirmed stability through RMSD, RMSF, Rg, PCA, DCCM, and FEL analysis. Immune simulations predicted robust responses, including high IgG1 titers. Codon optimization (GC content 56.62%) and cloning confirmed expression potential.

The V2 construct exhibits stability, strong immunogenicity, and broad population coverage, supporting its potential as a vaccine candidate against SEOV. Experimental validation in vitro and in vivo is required to confirm efficacy and safety.