Vaccine Development for Zika Virus—Timelines and Strategies

Abstract

Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and Central America in 2015 to 2016. Microcephaly has been causally associated with Zika virus infection during pregnancy and the World Health Organization declared Zika virus as a Public Health Emergency of International Concern. To address this crisis, many groups have expressed their commitment to developing a Zika virus vaccine. Different strategies for Zika virus vaccine development are being considered including recombinant live attenuated vaccines, purified inactivated vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika virus vaccine development will be the target group chosen for vaccination and which end point(s) is chosen for efficacy determination. The first clinical trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway to licensure for a Zika virus vaccine is expected to take several years. Efforts are ongoing to accelerate Zika virus vaccine development and evaluation with the ultimate goal of reducing time to licensure.

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

“…Recent studies have established that candidate anti-ZIKV vaccines can protect against viremia, tissue viral burden, and/or lethal challenge in mice or non-human primate models of ZIKV infection and pathogenesis (Abbink et al, 2016; Dowd et al, 2016b; Larocca et al, 2016; Muthumani et al, 2016; Pardi and Weissman, 2017; Richner et al, 2017; Shan et al, 2017a). Several of these ZIKV vaccine platforms (DNA plasmid or modified mRNA LNPs encoding prM-E gene and chemically inactivated virions) have advanced to phase 1 human trials (Durbin, 2016). However, all of the pre-clinical studies have been performed in non-pregnant animals, and thus vaccine-mediated protection against placental and fetal infection and injury has not been demonstrated.…”

“…While several of these vaccine candidates have advanced to phase 1 clinical trials in humans (Durbin, 2016), no study has established vaccine protection in the context of pregnancy.…”

In Vitro Assembly and Stabilization of Dengue and Zika Virus Envelope Protein Homo-Dimers

“…The continuing threat of DENVs and, more recently, ZIKV has stimulated much work on different vaccine platforms including live attenuated virus, inactivated whole virus, protein subunit and DNA vaccines 4–12 . The congenital malformations caused by ZIKV infection during pregnancy has stimulated work on subunit vaccines, as live attenuated and other replicating virus vaccines are contraindicated during pregnancy.…”

Vaccination strategies against Zika virus

“…Remarkably, in less than one year, several of these vaccines have progressed beyond pre-clinical studies in animals and are advancing into phase 1 human trials (Table 1). Additional platforms (e.g., live-attenuated vaccines) are in pre-clinical testing and expected to enter human trials in 2017 [57]. …”

“…Several groups have stated an intention of developing live-attenuated ZIKV vaccines although to date, no data showing immunogenicity or protection has yet been published [57]. Even if such vaccines were highly immunogenic, questions remain as to their relative safety in some of the target populations.…”