Dengue Human Infection Model Performance Parameters

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 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. DENV illness results from a complex interaction of viral properties and host immune responses. Dengue vaccine development efforts are challenged by immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays. A dengue human infection model (DHIM) will be an essential tool in developing potential dengue vaccines or antivirals. The potential performance parameters needed for a DHIM to support vaccine or antiviral candidates are discussed.