Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine

Abstract

Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

Figure 1

Structure of the flavivirus genome and genetic distance of selected flaviviruses. (a). Genomic structure and polyprotein processing of flaviviruses. The positive-sense RNA genome forms a single open-reading frame that is translated into a polyprotein precursor containing three structural proteins (blue) and seven NS proteins (yellow) flanked by the 5′ and 3′ UTRs. Cleavage sites for the host-cell signalase and furin, and the viral NS2B/NS3 protease as well as an unidentified protease are indicated by arrows. The functions of the NS3 and NS5 proteins that are required for RNA replication and polyprotein processing are also shown. (b). Phylogenetic analysis of selected flaviviruses. A neighbor-joining tree was compiled with complete genome sequences of DENV, JEV, and YFV available in the GenBank database using a Kimura two-parameter model. Sequence alignment and phylogenetic analysis were performed with MEGA 6 software(Oxford, UK) Virus sequences included are DENV-1 Hawaii, DENV-2 16681, DENV-3 H87, DENV-4 H241, JEV JaOArS982, and YFV ASIBI.