Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
University of Chinese Academy of Sciences, Beijing, China.
J Infect Dis. 2024 Jan 12;229(1):43-53. doi: 10.1093/infdis/jiad238.
West Nile virus (WNV), an arthropod-borne flavivirus, can cause severe symptoms, including encephalitis, and death, posing a threat to public health and the economy. However, there is still no approved treatment or vaccine available for humans. Here, we developed a novel vaccine platform based on a classical insect-specific flavivirus (cISF) YN15-283-02, which was derived from Culicoides. The cISF-WNV chimera was constructed by replacing prME structural genes of the infectious YN15-283-02 cDNA clone with those of WNV and successfully rescued in Aedes albopictus cells. cISF-WNV was nonreplicable in vertebrate cells and nonpathogenic in type I interferon receptor (IFNAR)-deficient mice. A single-dose immunization of cISF-WNV elicited considerable Th1-biased antibody responses in C57BL/6 mice, which was sufficient to offer complete protection against lethal WNV challenge with no symptoms. Our studies demonstrated the potential of the insect-specific cISF-WNV as a prophylactic vaccine candidate to prevent infection with WNV.
西尼罗河病毒（WNV）是一种虫媒黄病毒，可引起严重症状，包括脑炎和死亡，对公共卫生和经济构成威胁。然而，目前仍然没有针对人类的批准治疗或疫苗。在这里，我们开发了一种基于经典昆虫特异性黄病毒（cISF）YN15-283-02 的新型疫苗平台，该病毒源自库蠓。通过用 WNV 的 prME 结构基因替换传染性 YN15-283-02 cDNA 克隆的 prME 结构基因，构建了 cISF-WNV 嵌合体，并在白纹伊蚊细胞中成功拯救。cISF-WNV 在脊椎动物细胞中不能复制，在 I 型干扰素受体（IFNAR）缺陷型小鼠中无致病性。单次免疫 cISF-WNV 可在 C57BL/6 小鼠中引起相当大的 Th1 偏向性抗体反应，足以提供针对致命 WNV 挑战的完全保护而无任何症状。我们的研究表明，昆虫特异性 cISF-WNV 作为预防 WNV 感染的预防性疫苗候选物具有潜力。
