Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo–electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 10^9.5 cell culture infectious dose/ml or ≈7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR^−/− mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.

诸如登革热，黄热病，寨卡病毒，西尼罗河病毒和日本脑炎病毒等黄病毒对全球健康构成沉重负担。正在寻求新的疫苗以解决与当前的减毒活疫苗相关的安全性和生产问题。在这里，我们描述了一种新的昆虫特异性黄病毒Binjari病毒，该病毒对与上述病原性脊椎动物感染性黄病毒（VIFs）的结构蛋白基因（prME）的交换具有显着的耐受性。嵌合BinJ / VIF-prME病毒在脊椎动物细胞中仍然具有复制缺陷，但在蚊子细胞中可以高效复制。低温电子显微镜和单克隆抗体结合研究表明，嵌合BinJ / VIF-prME病毒颗粒在结构和免疫学上与其亲本VIF相似。^9.5细胞培养物的感染剂量/ ml或≈7mg / L。BinJ / VIF-prME病毒在诊断（使用人和马血清检测的微球免疫测定和ELISA）和疫苗应用（说明在鼠IFNAR ^-/-小鼠模型中抵抗Zika病毒攻击的保护）中显示出实用性。因此，BinJ / VIF-prME病毒代表了一种通用的，非传染性的（对于脊椎动物细胞而言），高产量的技术，可用于产生生物含量要求低的嵌合黄病毒颗粒。