Abstract
The co-infection of DENV-1 and DENV-3 during endemic outbreaks can be potentially fatal and complicate the diagnostic process. In our study, we have focused on the development of a multiepitope vaccine against DENV-1 and DENV-3 co-infection, utilizing non-structural protein 1 (NS1) and envelope protein (E) as key antigens. B cell and T cell epitopes were predicted for their immunogenicity, antigenicity, and ability to elicit an IFN-γ response. The final construct showed predicted stability (Instability Index: 30.63), antigenicity (0.5509), non-allergenicity, and hydrophilic character (GRAVY: −0.226) based on computational assessments. Tertiary structural validation revealed 90.1% of residues in a favoured region. Molecular docking revealed a stronger binding of the DENV-TLR3 complex. The receptor and vaccine have stable interactions, according to molecular dynamics simulations and free energy estimations (-90 kJ/mol). Strong B and T cell memory responses were demonstrated by immune simulations, accompanied by increased levels of IgG, IFN-γ, and TGF-β. The codon-optimized sequence was successfully cloned into the pcDNA™3.1/V5-His-TOPO® expression vector for potential experimental validation. As a result of this in silico approach, a targeted vaccine for DENV-1 and DENV-3 co-infections is possible, which merits further experimental evaluation.
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The authors acknowledge Nitte (Deemed to be University) for providing research facilities.
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This project was supported by the Department of Science and Technology, Government of India (Grant No. TDP/BDTD/31/2021(G)), and Nitte (Deemed to be University) (Grant No. NUFR118B-112).
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Deepthi Ishwar: Methodology, Data curation, Formal analysis and Writing – original draft. Shruthi Padavu: Methodology and Data curation. Manish Kumar: Methodology. Pavan Gollapalli: Data curation, Formal analysis and Writing – review & editing. Ballamoole Krishna Kumar: Data curation, Formal analysis and Writing – review & editing. Anoop Kumar: Methodology, Data curation, Formal analysis and Writing – review & editing. Praveen Rai: Data curation, Formal analysis, Conceptualization and Writing – review & editing.
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Ishwar, D., Padavu, S., Kumar, M. et al. In silico design of a multi-epitope vaccine targeting DENV-1 and DENV-3. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35678-0
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DOI: https://doi.org/10.1038/s41598-026-35678-0


