A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice.

Jessamine E Hazlewood,Laura J Vet,Bing Tang,Roy A Hall,Daniel J Rawle,Andreas Suhrbier,Kexin Yan,Eri Nakayama,Jody Hobson-Peters

doi:10.3390/vaccines8030496

Abstract

Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), a spectrum of birth defects that can lead to life-long disabilities. A range of vaccines are in development with the target population including pregnant women and women of child-bearing age. Using a recently described chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV), we generated a ZIKV vaccine (BinJ/ZIKA-prME) and illustrate herein its ability to protect against fetal brain infection. Female IFNAR−/− mice were vaccinated once with unadjuvanted BinJ/ZIKA-prME, were mated, and at embryonic day 12.5 were challenged with ZIKVPRVABC59. No infectious ZIKV was detected in maternal blood, placenta, or fetal heads in BinJ/ZIKA-prME-vaccinated mice. A similar result was obtained when the more sensitive qRT PCR methodology was used to measure the viral RNA. BinJ/ZIKA-prME vaccination also did not result in antibody-dependent enhancement of dengue virus infection or disease. BinJ/ZIKA-prME thus emerges as a potential vaccine candidate for the prevention of CSZ.

Highlights

Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), which encompasses a range of birth defects associated with ZIKV infection of the mother during pregnancy and transplacental infection of the fetus
We show that BinJ/ZIKA-pre-membrane and envelope coding sequence (prME) vaccination protects against viremia and fetal brain infection in
ZIKVPRVABC59 was recovered by transfection of Vero E6 cells and virus stocks were generated in C6/36 cells

Summary

Introduction

Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), which encompasses a range of birth defects associated with ZIKV infection of the mother during pregnancy and transplacental infection of the fetus. ZIKV a Public Health Emergency of International Concern from February to November 2016, with a range of vaccines against ZIKV currently in development [3]. As pregnant women and/or women of child bearing age are the key targets for vaccination, heightened safety concerns might lead to a preference for inactivated, subunit, or modified RNA vaccines rather than live, live-attenuated, or live virus-vectored vaccines [4,5,6,7,8]. Use of vaccine adjuvants during pregnancy may raise safety concerns [5,6]. Live-attenuated chimeric flavivirus vaccines are well established and generally use an attenuated flavivirus vaccine as a backbone, with the latter’s pre-membrane and envelope coding sequence (prME)

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