Antigenic cross-reactivity between Zika and dengue viruses: is it time to develop a universal vaccine?

Zika and the four serotypes of dengue are closely related flaviviruses that share a high degree of structural and sequence homology and co-circulate in many regions of the world. Here, we review recent studies investigating antigenic cross-reactivity between the two viruses. We discuss the pathogenic and protective roles of cross-reactive anti-viral antibody and T cell responses, respectively, in modulating the outcome of secondary dengue or Zika infection. Based on recent findings and increased incidence of severe disease in seronegative recipients of the first dengue vaccine to be licensed, we propose that the time has come to focus on developing pan-flavivirus vaccines that protect against Zika and four dengue serotypes by eliciting protective cross-reactive T cell responses while concomitantly reducing production of cross-reactive antibodies that can exacerbate disease.