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Nature:新疫苗让疟原虫自我毁灭

2020-04-23 唐一尘 中国科学报

4月22日,《自然》发表的一项研究显示,研究人员筛选了对严重疟疾有天然免疫抵抗力的儿童的血液样本,发现了一种针对特殊疟疾蛋白质PfGARP的抗体,这种抗体似乎可以保护儿童免受严重疟疾的侵害。

4月22日,《自然》发表的一项研究显示,研究人员筛选了对严重疟疾有天然免疫抵抗力的儿童的血液样本,发现了一种针对特殊疟疾蛋白质PfGARP的抗体,这种抗体似乎可以保护儿童免受严重疟疾的侵害。

疟疾是一种由蚊子传播的寄生虫病,每年夺去近50万人的生命。以前开发抗疟疾疫苗的努力仅取得了有限的成功。

该研究历时近20年,始于美国国立卫生研究院的Michal Fried和Patrick Duffy领导的流行病学研究。从2001年起,他们开始在坦桑尼亚招募一批儿童。这些孩子一出生就被纳入研究,研究人员对他们进行了多年的跟踪观察,看他们当中谁对疟疾产生了自然获得性免疫应答。

最后,Kurtis团队从坦桑尼亚队列中选择了12名耐药和14名易感儿童。研究人员观察了从2岁左右的儿童身上采集的血液样本,这一年龄段的儿童似乎就出现了自然获得性免疫。研究人员利用一种复杂的方法将疟疾蛋白一个接一个地引入每个血液样本,以便寻找存在于免疫样本而非易感样本中的特定蛋白的任何抗体,结果发现PfGARP是造成抵抗性的一个潜在因素。

实验室测试表明,PfGARP抗体似乎激活了疟疾的自毁机制,导致寄生在人类红细胞内的寄生虫经历一种程序化的细胞死亡。之后,研究人员在246名儿童的大样本中检测了抗体对PfGARP的反应是否与免疫性相关。他们发现,没有抗PfGARP抗体的儿童患严重疟疾的风险是有抗体的儿童的2.5倍。

研究人员说,人类疫苗试验可能还要数年,而且无法确定它是否会有效。但是,研究小组表示,有理由相信,这种新策略可能会在其他人失败的地方取得成功。这是因为它在感染周期中与其他疫苗在不同的时间攻击寄生虫。

一种针对第一阶段——旨在预防肝脏感染——的现有疫苗效果有限。Kurtis说,部分原因是干预的时间窗口太小了。“寄生虫从蚊子到肝脏只需要5分钟。”他说。“因为它非常快,需要大量抗体阻止它。如果只有一个孢子进入,你就得了疟疾。”

而这种新疫苗针对的是滋养体阶段,这一阶段最多能持续一天。研究人员希望,干预时间越长,杀死寄生虫所需的抗体量就越少,从而研制出更有效的疫苗。

原始出处:

Raj, D.K., Das Mohapatra, A., Jnawali, A. et al. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature (2020). https://doi.org/10.1038/s41586-020-2220-1.

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    2020-08-27 14818eb4m67暂无昵称

    学习了

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    2020-07-06 liye789132251
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    2020-05-27 gous
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