Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore.
Programme in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore.
Nat Commun. 2018 Mar 12;9(1):1031. doi: 10.1038/s41467-018-03337-2.
Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.
Zika 病毒（ZIKV）是一种黄病毒，可导致先天性疾病，因此需要开发有效的长期预防策略。具有类似于黄热病 17D（YF17D）减毒活疫苗（LAV）特性的复制型 ZIKV 疫苗将是有利的，因为单次接种 YF17D 即可产生终身免疫力。然而，复制型 ZIKV 疫苗也必须安全，不会导致持续的器官感染。在这里，我们报告了一种开发 ZIKV LAV 的方法。我们鉴定出一种 ZIKV 变体，由于干扰素（IFN）限制的病毒增殖而产生小斑块，并且对内皮细胞的感染呈衰减。我们表明，这些特性共同降低了在小鼠模型中发生器官感染和垂直传播的风险，但仍具有足够的免疫原性以预防野生型 ZIKV 感染。我们的研究结果为开发安全但有效的 ZIKV LAV 提供了一种策略。
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