Dengue human infection model: re-establishing a tool for understanding dengue immunology and advancing vaccine development.

Dengue is an emerging and re-emerging disease of the tropics and sub-tropics. Millions of infections occur annually exacting a significant social, financial, and health care resource toll. Widespread use of a safe and efficacious dengue vaccine in cooperation with strategic vector control is the best hope for reducing the global dengue burden. Despite over 100 y of research exploring dengue immunology, pathogenesis, animal models, and vaccine and drug development there is no licensed vaccine or dengue anti-viral. No correlate of protection or validated animal model of disease has been defined. Experimental human infection with partially attenuated dengue viruses are documented as early as 1902 and have facilitated research efforts resulting in seminal discoveries and observations. It is time to explore re-invigorating the dengue human infection model to support dengue vaccine development.