Recent Advances in Zika Virus Vaccine Development

Zika Virus (ZV) has infected over one million people worldwide. ZV crosses the placenta, infects developing fetus and causes Congenital Zika Virus syndrome (CZS) including microcephaly in newborns. In this up-to-date review, ZV immunology and vaccine development have been discussed with cutting edge advancement in this discipline. ZV belongs to flavivirus genus, shares structural similarities with Dengue Virus (DENV) that are the mainstay for vaccine development research and consists of positive-sense RNA, a capsid with an outer shell. Humoral immune response against ZV results in generation of neutralizing and cross-reactive antibodies. The neutralizing antibodies are produced against its pre-membrane (prM) and envelope (E) proteins, however, the cross-reactive antibodies may interact with the antigens of other flaviviruses in addition to ZV itself resulting in the antibody dependent enhancement (ADE) phenomenon, a risk for DENV immune ZV vaccine candidates. The vaccines developed against ZV include subunit and live-attenuated vaccines. Subunit vaccines are DNA, modified mRNA and virus-like particles (VLP) vaccines. DNA vaccine, developed by incorporating E protein antigen genetic code into the plasmid, is under different phases of clinical trials. Nucleoside-modified ZV prM-E mRNA vaccine, enveloped in lipid nano particles (LPN), has successfully been studied in mice and nonhuman primates. Live-attenuated 10-deletion vaccine, consisting of mutant viral RNA genome, activates cell-mediated and hum oral immune system. In conclusion, the ZV prospective vaccine must be safe enough for clinical trials, highly effective in generating neutralizing antibodies, free of ADE risk and compatible with variable transportation conditions. Keywords: Zika Virus structure; DNA vaccine; modified mRNA vaccine; Zika Virus vaccine