Mimicking live flavivirus immunization with a noninfectious RNA vaccine
Mimicking live flavivirus immunization with a noninfectious RNA vaccine
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DOI：
10.1073/pnas.0307145101
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发表时间：
2004-02-17
影响因子：
11.1
通讯作者：
Mandl, CW
中科院分区：
文献类型：
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作者：
Kofler, RM;Aberle, JH;Mandl, CW
黄病毒是具有世界医学重要性的人类病原体。它们最近受到了更多的关注，因为它们传播到了新的地区(如西尼罗河病毒传播到北美)，突显了它们作为新出现的疾病病原体的潜力。利用森林脑炎病毒，我们开发了一种新的基于自我复制但非传染性RNA的基因疫苗，并在小鼠身上进行了评估。这种RNA包含在宿主细胞中建立其复制机制所需的所有遗传信息，从而模拟自然感染。然而，衣壳蛋白编码区域的基因修饰同时阻止了传染性病毒颗粒的组装，并促进了非传染性亚病毒颗粒的分泌，从而产生中和抗体。这些特征表明，可以设计出新一代黄病毒疫苗，激发与活疫苗相同的先天和特异性免疫反应，但具有灭活疫苗的安全特征。
Flaviviruses are human pathogens of world-wide medical importance. They have recently received much additional attention because of their spread to new regions (such as West Nile virus to North America), highlighting their potential as newly emerging disease agents. Using tick-borne encephalitis virus, we have developed and evaluated in mice a new genetic vaccine based on self-replicating but noninfectious RNA. This RNA contains all of the necessary genetic information for establishing its replication machinery in the host cell, thus mimicking a natural infection. However, genetic modifications in the region encoding the capsid protein simultaneously prevent the assembly of infectious virus particles and promote the secretion of noninfectious subviral particles that elicit neutralizing antibodies. These characteristics demonstrate that a new generation of flavivirus vaccines can be designed that stimulate the same spectrum of innate and specific immune responses as a live vaccine but have the safety features of an inactivated vaccine.