Challenges in the clinical development of a dengue vaccine

•Dengue is the fastest spreading vector borne viral disease.•A vaccine would provide an important public health tool.•Vaccine candidates must demonstrate safety and efficacy in clinical trials.•Study sites must ensure high quality, long term surveillance.•Appropriate preparation and community engagement are critical.

Dengue is a potentially fatal viral disease for which treatment is limited to supportive care, and prevention and control are based on mosquito vector control programs. It is the fastest growing arboviral infection and is currently endemic in more than 100 tropical and subtropical countries, placing over 40% of the world's population at risk. At least 50 million infections are thought to occur annually, resulting in approximately 500 000 hospitalizations, mainly in children. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. This review considers some of the challenges to dengue vaccine development, and in particular the challenges of demonstrating dengue vaccine efficacy.