Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA
Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA
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DOI：
10.1016/j.jconrel.2015.04.001
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发表时间：
2015-06-10
影响因子：
10.8
通讯作者：
Zeng, Mingtao
中科院分区：
文献类型：
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作者：
Li, Junwei;Arevalo, Maria T.;Zeng, Mingtao
接种减毒活疫苗是预防传染病的有效途径。虽然使用了几种方法来制造它们，但有效性和安全性仍然是一个挑战。在这项研究中，我们评估了创建一种表达功能性物种特异性人工microRNA的自减毒RNA病毒的可行性。以流感病毒为模型，我们生产了一种减毒病毒，该病毒携带哺乳动物特异性miR-93表达盒，从非结构（NS）基因片段的插入位点表达病毒核蛋白（NP）特异性人工microRNA。由此产生的工程化减毒流感病毒PR8-amiR-93NP在哺乳动物细胞中产生成熟和功能性的人工microRNA，而在禽类细胞中则没有。此外，与野生型相比，PR8-amiR-93NP在小鼠体内的毒性降低了104倍。重要的是，PR8-amiR-93NP鼻内免疫赋予了对异源流感病毒株的交叉保护免疫。总之，这种方法为RNA减毒活疫苗的研制提供了一个安全有效的平台。(C) 2015 Elsevier B.V.版权所有
Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 104 fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines. (C) 2015 Elsevier B.V. All rights reserved.