Abstract
Hantavirus is a rodent-borne zoonotic pathogen causing Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS), with substantial global morbidity and mortality. No universally approved human vaccine exists, making a safe, effective vaccine a public health priority. An immunoinformatics strategy was used to design a multi-epitope vaccine construct (MEVC) targeting the glycoprotein precursor (GP_HANTL) of Hantaan orthohantavirus. Cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes were predicted and screened for antigenicity, immunogenicity, MHC-binding affinity, and population coverage. Selected epitopes were joined with EAAAK, AAY, GPGPG, and KK linkers and fused to a β-defensin adjuvant. The construct was evaluated by physicochemical characterization, structural modeling, molecular docking, molecular dynamics (MD) simulation, immune simulation, codon optimization, and in silico cloning. The final construct comprised 10 CTL, 10 HTL, and 5 B-cell epitopes, with 99.24% global population coverage. Structural validation showed 95% of residues in favored Ramachandran regions and an ERRAT score of 82. Molecular docking produced a favorable ClusPro score (− 1273.6) for the selected MEVC–TLR4 complex. Immune simulations predicted robust humoral and cellular responses, including elevated antibodies, memory B cells, and CTL/HTL activation. Codon optimization yielded a CAI of 0.94, supporting efficient Escherichia coli expression. A 100-ns MD simulation showed substantial conformational adaptation of the MEVC while TLR4 remained comparatively stable; accompanying Rg and SASA trends indicated that the MEVC adopted a more compact state during the trajectory. The proposed MEVC demonstrated favorable predicted immunogenicity, favorable structural characteristics, broad population coverage, and favorable expression characteristics. These findings support experimental validation and development of a preventive strategy against Hantavirus infection.
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Data availability
The data generated and analysed during this study are included in this published article. Additional computational data supporting the findings of this study are available from the corresponding author upon reasonable request.
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S.U. conceived and designed the study, performed the computational analyses, interpreted the data, prepared the figures, and wrote the original draft of the manuscript. A.T., C.E.M.R., S.A., S.K., T.J.T., M.M.H and SU. contributed to data interpretation, methodology, and critically reviewed and reviewed the manuscript. S. U conceived and supervised the study, provided scientific guidance and resources, A.A critically reviewed the manuscript, and approved the final version. All authors read and approved the final manuscript.
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Ullah, S., Tonks, A., Maya-Ramírez, C.E. et al. Integrated immunoinformatics and molecular dynamics approaches reveal a promising multi-epitope vaccine against hantavirus. In Silico Pharmacol. 14, 273 (2026). https://doi.org/10.1007/s40203-026-00782-6
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DOI: https://doi.org/10.1007/s40203-026-00782-6