Nature:中国团队开发重组蛋白新冠疫苗,已在非人灵长类模型中证实预防潜力

2020-07-30 佚名 学术经纬

一篇关于新冠疫苗的最新论文,研发团队开发出一款重组蛋白候选新冠疫苗。在非人灵长类等动物模型中完成的实验表明,这款疫苗能诱发强烈的针对SARS-CoV-2的保护性免疫应答和病毒中和抗体。

《自然》(Nature)杂志在线发表了一篇关于新冠疫苗的最新论文。四川大学华西医院生物治疗国家重点实验室魏霞蔚研究员,逯光文研究员和澳门科技大学医学院张康教授为共同通讯作者。研发团队开发出一款重组蛋白候选新冠疫苗。在非人灵长类等动物模型中完成的实验表明,这款疫苗能诱发强烈的针对SARS-CoV-2的保护性免疫应答和病毒中和抗体。

研究作者在论文中提到,新冠病毒使用其刺突蛋白的受体结合域(RBD)与宿主细胞的受体血管紧张素转化酶2(ACE2)相结合,是其感染过程中最关键的步骤。在设计疫苗时,为了在激发最大的免疫原性同时,尽可能减少潜在的副作用,研究人员设想找出最小的刺突蛋白片段作为抗原。

在本研究中,科学家们使用S蛋白的多个不同部分制作了多款候选疫苗,经过测试和比较,他们最终确认,相比S蛋白的细胞外结构域蛋白(ECD)、S1亚基和S2亚基,RBD作为免疫原有最大的病毒中和活性。因此,研究小组最终使用了RBD中编号为319-545的一段氨基酸序列,用以产生抗原。

为生产这些重组蛋白,研究小组采用了杆状病毒表达载体系统进行蛋白表达。论文中指出,这种技术产生的疫苗通常具有正确折叠的蛋白质构象,并且适用于商业规模的疫苗生产,已经在一些获批上市的宫颈癌疫苗和流感疫苗产品中有所使用。

在重组RBD蛋白候选疫苗的动物实验中,小鼠、兔子和猕猴在仅仅接受一次注射的7天或14天后,血清中已经可以看到,它们体内针对重组RBD的IgG和IgM抗体开始升高。除了重组RBD蛋白本身可以有效地诱导特异性抗体的产生外,实验显示,添加佐剂后可以显着增强诱导作用,产生更高水平的特异性抗体。

体外细胞实验显示,从免疫动物身上取得的血清,可以阻断RBD与细胞表面表达的ACE2相结合,并且几乎百分之百中和SARS-CoV-2假病毒(只有病毒外壳而没有病毒核酸)。

更重要的是,在非人灵长类动物模型的攻毒实验中,这款候选疫苗显示出了阻断新冠病毒感染的保护作用。研究人员以每剂20 μg或40 μg的剂量相隔7天分两次给猕猴进行了接种。而后,在首次接种疫苗的28天使它们接触活的新冠病毒。接种疫苗的猕猴体内可以检测到针对活病毒的中和抗体,它们获得了完全的保护,无论是咽拭子还是肺组织中,都没有检测到病毒核酸。相反,接受生理盐水或仅接受佐剂注射的两个对照组,动物们出现了明显的病毒感染迹象。

值得一提的是,这些动物实验还表明,这款重组RBD候选疫苗没有触发抗体依赖性增强(ADE)作用或引起新冠肺炎

研究人员在论文最后总结道,这款候选疫苗的相关研究“凸显了新冠疫苗设计中S蛋白RBD结构域的重要性,并为诱导针对RBD的抗体开发疫苗提供了依据”。此外,研究人员认为,利用重组蛋白的疫苗生产技术在大规模供应和商业上都有可行的先例,这些特点可以为这款候选疫苗的进一步开发提供支持。

原始出处:

Jingyun Yang, Wei Wang,Xiawei Wei,et al.A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.Nature,Published: 29 July 2020

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    2020-12-15 liye789132251
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    2021-04-22 lg.zhao
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    2020-08-01 xqptu
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    2020-07-30 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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    2020-07-30 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0

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