Zika Virus: Immunity and Vaccine Development

Abstract

The emergence of Zika virus in the Americas and Caribbean created an urgent need for vaccines to reduce transmission and prevent disease, particularly the devastating neurodevelopmental defects that occur in utero. Rapid advances in Zika immunity and the development of vaccine candidates provide cautious optimism that preventive measures are possible.

Figure 1. Multiple platforms for a protective ZIKV vaccine

The emergence and rapid spread of ZIKV has created an urgent need for a safe effective ZIKV exists. Multiple vaccine platforms, guided by considerable experience with other flaviviruses, are being developed and tested in clinical studies. Gene-based vaccine approaches including nucleic acid (DNA or mRNA) or other viral vector expression platforms provide a rapid means to introduce viral antigens of any sequence into the candidate vaccine. ZIKV vaccines encoding the structural proteins M-E and prM-E have been developed. Expression of prM-E in vitro results in the production subviral particles that traffic through the secretory pathway and undergo virion maturation in an analogous process to infectious virions (inset), resulting in a particulate antigen. The manner in which E is presented following transfection of M-E, and whether this is secreted from cells, remains unknown. ZIKV purified inactivated virions (ZPIV) have been developed and show excellent immunogenicity in preclinical studies. Finally, live-attenuated virus approaches developed for DENV vaccines can be adapted for ZIKV including chimeric viruses encoding ZIKV structural proteins in a DENV or YFV backbone or ZIKV attenuated by genetic modifications are also being developed. This cost effective approach, if successful, has the potential to be combined with other live-attenuated flavivirus vaccines.