Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
Beijing Shunlei Biotechnology Co. Ltd., Beijing, China.
EMBO Mol Med. 2021 Sep 7;13(9):e14108. doi: 10.15252/emmm.202114108. Epub 2021 Aug 5.
The genus Flavivirus comprises numerous emerging and re-emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live-attenuated vaccine (LAV), WNV-poly(A), by replacing 5' portion (corresponding to SL and DB domains in WNV) of 3'-UTR with internal poly(A) tract. WNV-poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single-dose vaccination elicited robust and long-lasting immune responses, conferring full protection against WNV challenge. Such "poly(A)" vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.
黄病毒属包括许多新发和再发的虫媒病毒，可导致人类疾病。疫苗是预防黄病毒病的最佳方法。但是，当面临不可预测的黄病毒爆发时，病原体的多样性一直是及时开发新疫苗的主要障碍之一。我们使用西尼罗河病毒（WNV）作为模型，通过用内部 poly(A) 结构替换 3'-UTR 的 5' 部分（WNV 中的 SL 和 DB 结构域），开发了一种新的减毒活疫苗（LAV）WNV-poly(A)。WNV-poly(A)不仅在 Vero 细胞中高效繁殖，而且在小鼠模型中高度减毒。单次接种可引起强烈且持久的免疫反应，完全可预防 WNV 攻击。由于该策略针对黄病毒的普遍靶区，因此这种“poly(A)”疫苗策略在黄病毒减毒活疫苗的开发中具有广阔的应用前景。
