Vaccine development as a means to control dengue virus pathogenesis: Do we know enough?

Dengue virus (DENV) is a mosquito-transmitted RNA virus responsible for 390 million infections each year and significant morbidity and mortality throughout tropical and subtropical regions of the world. Efforts to develop a DENV vaccine span 70 years and include the work of luminaries of the virus vaccine field. Although vaccines have been used to reduce the global health burden of other flaviviruses, the unique requirement for a single vaccine to protect against four different groups of dengue viruses, and the link between secondary infections and DENV disease pathogenesis, has limited success to date. In this review, we discuss several promising DENV vaccine candidates in clinical trials and assess how recent advances in understanding of DENV biology and immunity may expedite efforts toward the development of safe and effective vaccines.