Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo, Louis D.; Gambotto, Andrea

One thing that we learned in the presented ZIKV vaccine studies is that the yield of production of the ZIKV envelope E subunit protein was very low in the current format. This finding, also confirmed by a recently published ZIKV vaccine study , is similar to what was previously observed for other flaviviruses (Taylor et al., 2016) . The low yield of E protein is probably due to the absence of preM, which is important for protein stability. For instance, expression of WNV E protein alone showed proteolytic cleavage compared to the E protein produced in the presence of preM (Taylor et al., 2016) . Thus, the inclusion of preM sequence seems to be an important prerequisite in ZIKV E-based vaccine development. Importantly, in this study, we used an immunocompetent mouse challenge model of ZIKV infection. This approach was inspired by a 1952 publication (Dick et al., 1952) in which ZIKV was shown to be pathogenic in newborn mice. Although this model does not recapitulate the ZIKV pathogenesis observed in humans, it is an effective model to evaluate the in vivo neutralizing activity of vaccine-induced ZIKV immunity. During the conduct of these experiments, many mouse models of ZIKV infection were established in interferon receptor-deficient mice and SJL mice (Cugola et al., 2016; Shah and Kumar, 2016; Miner et al., 2016; Dowall et al., 2016; Lazear et al., 2016; Rossi et al., 2016) . Further investigations in SJL mice, the closest clinical model of fetal microcephaly, will be considered to evaluate the efficiency of vaccine candidates here in the future.