Reverse Vaccinology Design of an Asian HLA-Targeted Multi-Epitope Vaccine Candidate Against HTNV Strain 76-118

HTNV remains a cause of hemorrhagic fever with renal syndrome, particularly in Asia, while broadly available vaccines remain limited. This study developed an Asian HLA-targeted multi-epitope vaccine candidate against HTNV strain 76-118 using reverse vaccinology and immunoinformatics. RdRp, GPC, and N proteins were screened for cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-cell epitopes using 42 representative Asian HLA alleles. Selected epitopes were evaluated for immunological and safety properties, followed by population coverage analysis, vaccine construction, immune simulation, structural modeling, molecular docking, 300 ns molecular dynamics simulation, MM-GBSA analysis, and in silico cloning. Twenty-five epitopes, comprising 10 CTL, 10 HTL, and 5 B-cell epitopes, were retained. Combined MHC class I and II predicted coverage averaged 95.15% across five regions and reached 99.29% in East Asia. Among four adjuvant-based constructs, the HBHA-containing vaccine was prioritized based on combined physicochemical and comparative immune-simulation characteristics. Docking with TLR4 yielded a predicted ΔG of −27.6 kcal mol−1, while trajectory-based MM-GBSA analysis produced a ΔGbind of −136.17 ± 3.14 kcal mol−1. Codon optimization achieved a CAI of 0.9640 and GC content of 52.27%. Collectively, these computational analyses identify the HBHA-based construct as a population-oriented HTNV vaccine candidate prioritized for subsequent experimental evaluation.