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The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti\u2010dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral\u2010vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host\u2010pathogen specific interaction, antibody\u2010dependent enhancement, cross\u2010reactive immunity among Flaviviruses, and host\u2010susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.<\/jats:p>","DOI":"10.1002\/rmv.2425","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:54:10Z","timestamp":1674449650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dengue determinants: Necessities and challenges for universal dengue vaccine development"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-2672","authenticated-orcid":false,"given":"Zahid","family":"Hussain","sequence":"first","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China (USTC)  Hefei China"},{"name":"CAS Key Laboratory for Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano\u2010Bionics (SINANO) Chinese Academy of Sciences  Suzhou 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