Live attenuated influenza virus vaccines by computer-aided rational design.

Live attenuated influenza virus vaccines by computer-aided rational design.
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DOI:
10.1038/nbt.1636
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发表时间:
2010-07
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
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--
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流感每年在全世界夺去25万至50万人的生命。尽管现有的疫苗和生物医学研究的巨大努力,这些惊人的数字在过去二十年中没有显着变化,激发了寻找新的,更有效的,可以快速设计和容易生产的疫苗。使用流感病毒株A/PR/8/34,我们描述了一个系统的,合理的方法,称为合成减毒病毒工程(SAVE),开发新的,有效的活减毒流感病毒候选疫苗,通过基因组规模的密码子对偏好的变化。减毒是基于病毒基因组中数百个核苷酸的变化,提供了高遗传稳定性和广泛的安全范围。该方法可以快速应用于任何新出现的流感病毒的整体,这一优势对于应对季节性流行病和大流行威胁,如H5 N1或2009-H1N1流感,具有重要意义。
Influenza claims 250,000 - 500,000 lives annually worldwide. Despite existing vaccines and enormous efforts in biomedical research, these staggering numbers have not changed significantly over the last two decades, motivating the search for new, more effective, vaccines that can be rapidly designed and easily produced. Using influenza virus strain A/PR/8/34, we describe a systematic, rational approach, termed Synthetic Attenuated Virus Engineering (SAVE), to develop new, efficacious live attenuated influenza virus vaccine candidates through genome-scale changes in codon pair bias. Attenuation is based on many hundreds of nucleotide changes across the viral genome, offering high genetic stability and a wide margin of safety. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is significant for dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza.
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