Prospects for a Zika Virus Vaccine

Abstract

A recent unprecedented outbreak of Zika virus (ZIKV) in the Americas has been associated with microcephaly and other congenital malformations in infants as well as Guillain-Barre syndrome in adults. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Promising data from preclinical vaccine studies in mice and monkeys suggest that an effective vaccine will likely be possible, but important scientific challenges remain. Here we review the current state of ZIKV vaccine development. We discuss different vaccination strategies and, in the context of what has been learnt from other flavivirus vaccines, we highlight challenges facing clinical evaluation of ZIKV vaccine candidates.

Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design

“…Thus, during ZIKV vaccine design, FL MAbs should be avoided. Thus far, many platforms have been developed for ZIKV vaccines (28), among which the mRNA vaccine candidate incorporates T76R, Q77E, W101R, and L107R mutations to destroy the FL. The modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of ADE during subsequent exposure to DENV, indicating the most potential for future clinical application (29).…”

Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope

“…The rapid spread of the virus, aided in part by its cellular tropism, diverse transmission modes, and ability to bypass the human type I interferon response, calls for the rapid development of effective countermeasures (Rodriguez-Morales et al, 2016). While an effective vaccine against ZIKV is still many years away (Barouch et al, 2017), monoclonal antibodies have shown promise in controlling infection in animal models (Sapparapu et al, 2016; Wang et al, 2016; Zhao et al, 2016), indicating that they could serve as a potential immunotherapy option for infected or at-risk individuals.…”

Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo

“…In the interim, sporadic outbreaks will likely occur in seronegative communities [51,52]. Immune sera from vaccine trials [78**] and passive immune therapies [41**,86], as well as candidate therapeutic compounds [87], could be tested in explant models of the human placenta and decidua for their ability to specifically prevent virus dissemination, as indicated by infection of Hofbauer cells and other surrogate markers of fetal infection [88*]. As previous work on HCMV infection of the human placenta greatly enabled our understanding of the early steps in ZIKV replication, ongoing testing in such models could enable responses to the emergence of new congenital viral diseases in the future.…”

“…Several groups have reported promising results from vaccine and passive antibody transfer studies in mice and non-human primates using multiple platforms [78**]. Five have reported DNA-based vaccines expressing pre-membrane and E proteins, which enable responses to quaternary epitopes known to elicit neutralizing activity [79–83]; all were shown to confer protection in animal models after virus challenge by various measures, including suppression of viremia and indicators of pathology.…”