Current issues in dengue vaccination

Abstract

Dengue is a global health problem and of concern to travelers and deploying military personnel, with development and licensure of an effective tetravalent dengue vaccine a public health priority. The recent performance of the lead dengue vaccine in a phase 2b efficacy trial underscores dengue vaccine development challenges. This review focuses on current issues in dengue vaccination. The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. Recent estimates on the burden of DENV infection determined that there are 390 million dengue infections per year, three times the current estimate by the WHO. There are no licensed antivirals or vaccines to treat or prevent dengue though many are in preclinical or clinical development. DENV illness results from a complex interaction of viral properties and host immune responses. Immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays are challenging dengue vaccine development efforts. Dengue vaccine development efforts have numerous complex challenges to overcome before a well tolerated and effective vaccine is licensed and available. In this review, the authors discuss the current issues in dengue vaccination.