The relevance of dengue virus genotypes surveillance at country level before vaccine approval

Abstract

Dengue is a major threat for public health in tropical and subtropical countries around the world. In the absence of a licensed vaccine and effective antiviral therapies, control measures have been based on education activities and vector elimination. Current efforts for developing a vaccine are both promising and troubling. At the advent of the introduction of a tetravalent dengue vaccine, molecular surveillance of the circulating genotypes in different geographical regions has gained considerable importance. A growing body of in vitro, preclinical, and clinical phase studies suggest that vaccine conferred protection in a geographical area could depends on the coincidence of the dengue virus genotypes included in the vaccine and those circulating. In this review we present the state-of-the-art in this field, highlighting the need of deeper knowledge on neutralizing immune response for making decisions about future vaccine approval and the potential need for different vaccine composition for regional administration.

Keywords: ADE, antibody-dependent enhancement; DC-SIGN, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; DENV, dengue viruses; E, envelope protein; Hsp70, heat shock protein 70; Hsp90, heat shock protein 90; M, membrane protein; MRCA, more recent common ancestor; NS1, non-structural protein 1; UTR, untranslated region; dengue virus; genotypes; neutralizing antibodies; ssRNA+, single-stranded positive-sense RNA viruses; surveillance; vaccines.

Figure 1.

Phylogenetic tree of the 4 DENV serotypes based on the complete (1479–1485 nt) envelope gene of 289 viral isolates worldwide. The intra-serotype genetic diversity has allowed the designation of genotypes within each DENV serotype.

Figure 2.

Global distribution of the different DENV genotypes. Strains of the different DENV genotypes circulating during the period 2001–2014 were included. The DENV strains from imported cases where disease establishment has not been demonstrated were excluded from the analysis.