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(See the major article by Kirkpatrick et al on pages 702–10.)

Dengue virus (DENV) represents a rapidly expanding global health threat, with approximately 40% of the world's population now living in >100 countries at risk for DENV transmission, including the United States [1, 2]. In 2010, an estimated 390 million DENV infections occurred worldwide, of which 96 million were symptomatic [3]. DENV infections produce a spectrum of clinical disease. This includes mild undifferentiated fever, classical dengue fever, and severe dengue [4]. Severe dengue is characterized by hemorrhage and/or plasma leakage (dengue hemorrhagic fever and dengue shock syndrome) and organ failure. Approximately 500 000 severe cases and 20 000 deaths are estimated to occur each year [1]. These syndromes can be caused by each of 4 antigenically distinct serotypes (DENV-1–4) that cocirculate throughout the Western Pacific, Southern and Southeast Asia, Africa, and the Americas [5, 6].

Owing to global warming, spread of the Aedes vector to many parts of the world, uncontrolled urbanization, and human travel, dengue continues to intensify in DENV-endemic areas and spread to previously unaffected areas. Multiple serotypes frequently cocirculate in areas of endemicity, and epidemics of different serotypes occur unpredictably from year to year. Because of the growing economic burden associated with DENV infections and the lack of effective vector-control measures or specific therapy, a licensed DENV vaccine has become an urgent need [7].

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