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 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ-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.

中文翻译：

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通过内部poly(A)大量替换3′UTR合理设计西尼罗病毒疫苗

黄病毒属包含许多引起人类疾病的新出现和重新出现的虫媒病毒。疫苗是预防黄病毒病的最佳方法。但面对不可预测的黄病毒爆发时，病原体多样性始终是及时开发新疫苗的主要障碍之一。我们以西尼罗河病毒（WNV）为模型，通过将3ʹ-UTR的5ʹ部分（对应WNV中的SL和DB结构域）替换为内部，开发了一种新型减毒活疫苗（LAV）WNV-poly(A)。聚（A）道。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。单剂量疫苗接种可引发强烈而持久的免疫反应，从而提供针对西尼罗河病毒攻击的全面保护。这种“poly(A)”疫苗策略可能有望在黄病毒LAV的开发中得到广泛应用，因为它在黄病毒中具有普遍的目标区域。