AN INVESTIGATION INTO ZIKA LIVE ATTENUATED VACCINE DEVELOPMENT

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus capable of vertical transmission, leading to the 2015-2016 microcephaly outbreak. The risks of fetal malformations and sexual transmission serve as great impetus for vaccine development to protect women of child-bearing age from infection during pregnancy. Particularly, live attenuated vaccines (LAVs) that are capable of inducing long-lasting immunity that withstand the long intervals between ZIKV outbreaks are much-needed. Using a ZIKV genetic variant isolated, we show that a systematic approach to screen for robust innate immune responses in monocyte-derived dendritic cells and attenuated infectivity in endothelial cells predicted safety and immunogenicity in an animal model. Furthermore, we demonstrate that vaccine viremia duration is a functional determinant of the magnitude of neutralizing antibody response and should thus be an important selection criterion for LAV candidates. Collectively, this thesis proposes a pathway for selection of safe and immunogenic ZIKV LAV candidates for further clinical development.