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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-\u03b3 response. The final construct showed predicted stability (Instability Index: 30.63), antigenicity (0.5509), non-allergenicity, and hydrophilic character (GRAVY: \u22120.226) 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\u00a0kJ\/mol). Strong B and T cell memory responses were demonstrated by immune simulations, accompanied by increased levels of IgG, IFN-\u03b3, and TGF-\u03b2. The codon-optimized sequence was successfully cloned into the pcDNA\u21223.1\/V5-His-TOPO\n                    <jats:sup>\u00ae<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-35678-0","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:22:59Z","timestamp":1768540979000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In silico design of a multi-epitope vaccine targeting DENV-1 and DENV-3"],"prefix":"10.1038","volume":"16","author":[{"given":"Deepthi","family":"Ishwar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi","family":"Padavu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Gollapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna Kumar","family":"Ballamoole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"35678_CR1","unstructured":"Report, W. 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