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研究人员利用空蛋白质外壳来模拟病毒外层结构开发新型疫苗

研究人员开发出口蹄疫新型疫苗

口蹄疫是在牛、羊、猪等偶蹄类动物间传播的一种病毒性传染病,若人类与患病动物接触过多,也有可能被感染。

近日,英国牛津大学等机构的研究人员宣布,成功开发出了一种口蹄疫新疫苗,这种疫苗在制作时不需活体病毒,因此更安全,更便于保存和运输。相关研究刊登在近期的《科学公共图书馆-病原卷》杂志上。

研究人员表示,传统的疫苗制作方法需要利用活体病毒,这增加了病毒在疫苗制造国传播的风险。他们在对口蹄疫病毒进行结构分析和计算机模拟研究的基础上,通过合成一种空的蛋白质外壳来模拟病毒外层结构。实验证明,这种合成外壳同样可以引发免疫反应。

研究人员随后对这种蛋白质外壳作出了相应调整,以增加疫苗的稳定性。实验显示,新疫苗可在56摄氏度的环境中,至少2小时保持稳定,这大大降低了疫苗储存、运输的难度及成本。

研究人员认为,口蹄疫新疫苗还为手足口病等类似病毒疫苗的研发提供了新思路,今后有望通过同样原理研发出针对类似病毒的新疫苗。

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Rational Engineering of Recombinant Picornavirus Capsids to Produce Safe, Protective Vaccine Antigen

PLoS Pathog, March 27, 2013 | doi:10.1371/journal.ppat.1003255

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.

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