Defeat Dengue and Zika Viruses With a One-Two Punch of Vaccine and Vector Blockade

Dengue virus (DENV) and Zika virus (ZIKV) are two mosquito-borne flaviviruses afflicting nearly half of the world population. Human infection by these viruses can either be asymptomatic or manifest as clinical diseases from mild to severe. Despite more cases are presented as self-limiting febrile illness, severe dengue disease can be manifested as hemorrhagic fever and hemorrhagic shock syndrome, and ZIKV infection has been linked to increased incidence of peripheral neuropathy Guillain-Barre syndrome and central neural disease such as microcephaly. The current prevention and treatment of these infectious diseases are either non-satisfactory or entirely lacking. Because DENV and ZIKV have much similarities in genomic and structural features, almost identical mode of mosquito-mediated transmission, and probably the same pattern of host innate and adaptive immunity toward them, it is reasonable and often desirable to investigate these two viruses side-by-side, and thereby devise common countermeasures against both. Here, we review the existing knowledge on DENV and ZIKV regarding epidemiology, molecular virology, protective immunity and vaccine development, discuss recent new discoveries on the functions of flavivirus NS1 protein in viral pathogenesis and transmission, and propose a one-two punch strategy using vaccine and vector blockade to overcome antibody-dependent enhancement and defeat Dengue and Zika viruses.