{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:08Z","timestamp":1791352208315,"version":"4.3.1"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Dengue virus remains a major global health threat due to its four antigenically diverse serotypes and limited treatment and vaccine options. This study aimed to design and evaluate a rational tetravalent multi-epitope vaccine capable of eliciting broad cross-serotype immune responses against dengue virus. An immunoinformatics-driven strategy was employed to identify CTL, HTL, and B-cell epitopes from the NS3, NS5, and envelope domain III proteins of DENV-1 to DENV-4 based on antigenicity, allergenicity, and predicted immunogenic potential, followed by assessment of HLA population coverage. Among the selected CTL epitopes, three were completely conserved across all four serotypes, while one HTL epitope showed the highest conservation among the selected MHC class II epitopes. High-scoring linear B-cell epitopes were identified across EDIII of all four DENV serotypes, with several closely matching experimentally validated epitopes and predominantly localizing to the FG loop and DIII\u2013DI hinge regions. The combined MHC class I and II population coverage reached 98.05% worldwide. The final vaccine construct comprised 584 amino acids incorporating 11 CTL, 14 HTL, and 7 B-cell epitopes linked to an N-terminal \u03b2-defensin adjuvant. Molecular docking, MM\/GBSA calculations, and 200 ns molecular dynamics simulations demonstrated stable interactions with both TLR2 and TLR4\/MD2 complexes, with docking binding energies of -16.2 and -26.0 kcal\/mol and MM\/GBSA binding free energies of -27.15\u00a0\u00b1\u00a00.54 and -52.50\u00a0\u00b1\u00a00.55 kcal\/mol, respectively.\n                    <jats:italic>In silico<\/jats:italic>\n                    immune simulation predicted substantial lymphocyte activation, enhanced IFN-\u03b3 secretion, predicted antigen clearance, and immunoglobulin class switching. Collectively, the proposed tetravalent multi-epitope vaccine was predicted to provide broad cross-serotype epitope representation, substantial population coverage, and favorable structural and immunological profiles, supporting its potential for further vaccine development. Experimental studies in appropriate\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models are warranted to further assess its immunogenicity, safety, and protective potential.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1934834","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:53:17Z","timestamp":1791348797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Design of a tetravalent dengue vaccine incorporating T-cell epitopes from NS3 and NS5 proteins and B-cell epitopes from the envelope protein using an immunoinformatics approach"],"prefix":"10.3389","volume":"16","author":[{"given":"Theerawat","family":"Dobutr","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Songkhla, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pemikar","family":"Srifa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Songkhla, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawamin","family":"Pinpathomrat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Songkhla, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"E4","DOI":"10.1038\/s41586-024-08416-7","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"636","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8040674","article-title":"The impact of serotype cross-protection on vaccine trials: DENVax as a case study","volume":"8","author":"Aguiar","year":"2020","journal-title":"Vaccines"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008676","article-title":"Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine","volume":"14","author":"Ahmed","year":"2020","journal-title":"PloS Negl.Trop. 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