Four dengue virus (DENV) serotypes are mosquito-borne flaviviruses of humans. The main mosquito vector of
DENV, Aedes aegypti, is difficult to control because urbanization and other human activities create environments
that strongly favor this species. Given the challenges of mosquito vector control and the absence of other effective
countermeasures, DENVs are thriving and infect several hundred million individuals, living in tropical and
subtropical regions of the world [1,2]. Highly effective vaccines have been developed against related flaviviruses such
as yellow fever (YFV), Japanese encephalitis (JEV) and tick-borne encephalitis (TBE) viruses [3]. The development
of DENV vaccines is more challenging because of the presence of four serotypes and the possibility of inadequate
immunity enhancing the replication of DENVs and thus, increasing the risk of severe disease [3]. Three live
attenuated tetravalent DENV vaccines are at different stages of testing in people. Most recently, the public health
community and vaccine developers faced a major setback when the leading candidate, Dengvaxia, was discovered
to have a safety signal in some children [4]. Furthermore, we recently discovered that dengue serotype 1 viruses
(DENV1) widely used for laboratory research are structurally different from DENV1 viruses circulating in the
plasma of those infected [5]. Here, we discuss our findings and the implications for DENV research and vaccines
