Developing a dengue vaccine: progress and future challenges.

Dengue is an expanding public health problem in the tropics and subtropical areas. Millions of people, most from resource-constrained countries, seek treatment every year for dengue-related disease. Despite more than 70 years of effort, a safe and efficacious vaccine remains unavailable. Antidengue antiviral drugs also do not exist despite attempts to develop or repurpose drug compounds. Gaps in the knowledge of dengue immunology, absence of a validated animal or human model of disease, and suboptimal assay platforms to measure immune responses following infection or experimental vaccination are obstacles to drug and vaccine development efforts. The limited success of one vaccine candidate in a recent clinical endpoint efficacy trial challenges commonly held beliefs regarding potential correlates of protection. If a dengue vaccine is to become a reality in the near term, vaccine developers should expand development pathway explorations beyond those typically required to demonstrate safety and efficacy.