Dengue: a growing threat requiring vaccine development for disease prevention

Abstract

Dengue disease is the most prevalent mosquito-borne viral infection in humans. At least one half of the global population is estimated at risk of infection and an estimated 390 million people are infected each year. Over the past few years, dengue burden continued to increase, mainly impacting developing countries. Alarming changes in dengue epidemiology were observed highlighting a spread from tropical to subtropical regions as well as urban to rural areas. An increase in the co-infections with the four serotypes has also been noticed, involving a shift in the targeted population from pediatric to adult. Facing these global changes, authorities will have to reinforce preventive actions and adapt healthcare management. New prophylactic strategies are urgently needed to prevent severe forms of dengue disease. The lack of specific antiviral therapies available turns vaccine development into a socio-economic challenge. In this review, we propose an update on the dengue global trends and different vaccine strategies in development. A particular attention will be paid to up-to-date information on dengue transmission and the protective efficacy of newly commercialized tetravalent dengue vaccine Dengvaxia®, as well as the most advanced candidate vaccines in clinical development.

Keywords: antiviral immunity; biological markers of dengue disease; clinical disease; dengue; epidemiology; live-attenuated viruses; prophylaxis; vaccine strategies.

Figure 1.

Evolution of epidemiological trends of outbreaks from 1990 to 2015. Dengue serotypes distribution: data based on 174 outbreaks including 80 from 2010 (46%) outbreaks distribution among WHO regions: data based on 262 outbreaks including 112 from 2010 (43%) (data from GUO et al, 2017).

Figure 2.

CYD-TDV (Dengvaxia®) vaccine. The tetravalent dengue vaccine CYD-TDV has been constructed by substituting prM and E genes from DENV-1 to DENV-4 into the backbone of the molecular clone of yellow fever vaccine YF-17D. there are four chimeric CYD-1 to CYD-4 which compose the CYD-TDV.

Figure 3.

TDV vaccine candidate. The Takeda tetravalent vaccine TDV has been generated by substituting prM and E genes from DENV-1, DEN-3, and DENV-4 into TDV-2 backbone. TDV2 is an over-attenuated mutant of DENV-2 vaccine candidate DENV-2-PDK53.

Figure 4.

LAV Delta 30 vaccine candidate. The tetravalent dengue vaccine LAV Delta 30 (or TV003) is composed of four mutants DENV-1 to DEN-4 which contain a deletion of 30 nucleotides (∆30) in the domain II of the 3ʹNTR of their genomic RNA. mutant DENV-4 virus ∆30 was used as a backbone to generate a chimeric DENV-2 virus ∆30 by substitution of the prM and E genes.