Prospects for the Development of a Dengue Vaccine

Dengue is a mosquito-borne viral disease which is currently an important and rapid growing health problem across the globe. Four closely related dengue serotypes cause the disease, which ranges from asymptomatic infection to undifferentiated fever, dengue fever (DF), and dengue hemorrhagic fever (DHF). Specific antiviral medications are not available for dengue and successful treatment, which is mainly supportive, depends on early recognition of the disease and careful monitoring for shock. Prevention of dengue depends on the control of the mosquito vector which has had only limited success. Development of a dengue vaccine is seen as a new tool to prevent this potentially fatal disease. The scope and intensity of dengue vaccine development has increased dramatically in the last decade. A live-attenuated tetravalent dengue vaccine based on chimeric yellow fever dengue virus, has progressed to licensure in several dengue endemic countries in 2015 after its phase III efficacy study involving more than 30,000 volunteers from Asia and Latin America. Several other dengue vaccine candidates are currently being evaluated in clinical and preclinical studies included other live attenuated vaccines, subunit, DNA purified inactivated vaccine candidates as well as virus-vectored and virus-like particle-based vaccines. Since dengue poses a heavy economic cost to the health system and society, the potential economic benefits are associated with promising dengue prevention interventions such as dengue vaccine and vector control innovations. in liver enzymes found in both children and adults indicates liver involvement during dengue infections. Pre-existing liver diseases which are more common in adults such as chronic hepatitis, alcoholic cirrhosis, and hemoglobinopathies can aggravate the liver impairment in dengue patients. Dengue with organ impairment mainly involves the liver and the central nervous system. Consistent hematological findings include vasculopathy, coagulopathy, and thrombocytopenia. Laboratory diagnosis includes virus isolation, serology, and detection of dengue ribonucleic acid. The age of dengue cases in several countries has increased from children to adolescents and adults. The pathogenesis of dengue infection is not well understood although antibody-dependent enhancement has been implicated in the pathogenesis [1]. Antiviral medications are not available for dengue and successful treatment, which is mainly supportive, depends on early recognition of the disease, bleeding tendency and careful monitoring for signs of circulatory failure. Adults have a higher prevalence of underlying diseases e.g. coronary artery disease, peptic ulcer, hypertension, diabetes mellitus, cirrhosis, or chronic kidney diseases, which should be considered in dengue management. A severity-based revised dengue classification for medical interventions has been developed and adopted in many countries [2]. Prevention using vector control has limited success, dengue vaccine is then seen as one of the major tools in effectively control dengue diseases [3,4]. Dengue vaccine development Dengue virus is a positive-sense, single stranded, 11kb RNA flavivirus consisting of three structural proteins (premembrane/ membrane (prM/M), envelope (E), and capsid (C) and seven nonstructural proteins. There are four antigenically distinct serotypes (DENV-1, 2, 3, and 4). The pathogenesis of DHF is not clearly Abbreviation DF: Dengue Fever; DHF: Dengue Hemorrhagic Fever; DSS: Dengue Shock Syndrome; Prm: Premembrane; M: Membrane; E: Envelope; C: Capsid; WHO: World Health Organization; CYD-TDV: Chimera Yellow Fever Dengue Tetravalent Dengue Vaccine; SAGE: Strategic Advisory Group of Experts; ADS: Asia Dengue Summit; ADVA: Asia Dengue Vaccination Advocacy; DVI: Dengue Vaccine Initiative; SEAMEO TROPMED: The Southeast Asian Ministers of Education Organization Tropical Medicine and Public Health; Fmx: Fondation Meriux; GDAC: Global Dengue and Aedestransmitted Diseases Consortium