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

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.

The host range restriction of bat-associated no-known-vector flaviviruses occurs post-entry

“…Classical ISFs were the first to be discovered and are phylogenetically distinct from all other flaviviruses, whereas dISFs phylogenetically affiliate with MBFVs, despite their apparent vertebrate-restricted phenotype. Chimeric viruses of ISFs and MBFVs have been created and characterized in order to identify the genetic determinants that condition the ISF host range restriction [39][40][41][42][43][44][45][46]. Chimeric MBFVs containing the prM-E genes of dISFs could not replicate in vertebrate cells, although viral antigen was produced [43].…”

Neuroinvasiveness of the MR766 strain of Zika virus in IFNAR-/- mice maps to prM residues conserved amongst African genotype viruses

“…The indicated tissues were collected at the indicated time points and homogenized in Eagle's minimal essential medium (Sigma Aldrich) containing 2% fetal bovine serum (FBS) using a tissue homogenizer and zirconia beads. The 50% cell culture infective dose (CCID 50 ) assays for serum and supernatants from homogenized tissues were performed as described previously [41][42][43][44][45][46][47][48][49][50]. Briefly, serum or supernatants from tissues were titrated in duplicate or quadruplicate in 5-or 10-fold serial dilutions on C6/36 cells.…”

Zika Virus Pathogenesis: A Battle for Immune Evasion

“…Taken together these data are key to understanding the biological processes, as well as the cellular and molecular mechanisms that could favor ZIKV maternal/fetal transmission and trafficking into the brain, as reported in ZIKV infected monocytes that present enhancing adhesion and transmigration capacities favoring viral dissemination to neural cells [ 368 ], in order to elicit fetal protection and develop antiviral therapeutics or vaccines [ 128 , 129 , 369 , 370 , 371 , 372 ].…”