Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.
Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.
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DOI：
10.1016/j.virol.2015.10.015
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
V. Yamshchikov;M. Manuvakhova;E. Rodriguez
中科院分区：
文献类型：
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作者：
V. Yamshchikov;M. Manuvakhova;E. Rodriguez
由于西尼罗病毒NY 99株的高毒力和致病性，直接减毒用于疫苗开发的目的是不可行的。相反，我们创建了具有NY 99血清学同一性的高度减毒嵌合病毒W1806。为了进一步减毒W1806，我们研究了在日本脑炎病毒疫苗SA 14 -14-2中发现的突变的影响。携带所有减毒突变的WN病毒在哺乳动物中失去了感染性，但在蚊子细胞中没有。没有一个单一的逆转恢复哺乳动物细胞的感染性，虽然蚊子细胞的感染性增加，观察。为了鉴定适合进一步减毒W1806的突变子集，我们分析了E138 K和K279 M变化对衍生化W 956的毒力、生长特性和免疫原性的影响，嵌合W1806从衍生化W 956继承其生物学特性和减毒谱。尽管有很强的显性减毒作用，但仅引入两个突变不足以将W1806减毒至人类使用可接受的安全水平。
Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use.