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ABSTRACTIntroductionFrom both a public health and economic perspective, vaccination is arguably the most effective approach to combat endemic and pandemic infectious diseases. Dengue affects more than 100 countries in the tropical and subtropical world, with 100–400 million infections every year. In the wake of the recent setback faced by Dengvaxia, the only FDA-approved dengue vaccine, safer and more effective dengue vaccines candidates are moving along the clinical pipeline.Area coveredThis review provides an update of the latest outcomes of dengue vaccine clinical trials. In the light of recent progress made in our understanding of dengue pathogenesis and immune correlates of protection, novel vaccine strategies have emerged with promising second-generation dengue vaccine candidates. Finally, the authors discuss the dengue-specific challenges that remain to be addressed and overcome.Expert opinionThe authors propose to explore various adjuvants and delivery systems that may help improve the design of safe, effective, and affordable vaccines against dengue. They also challenge the concept of a ‘universal’ dengue vaccine as increasing evidence support that DENV strains have evolved different virulence mechanisms.