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Science Translational Medicine:mRNA疫苗进入全新领域,预防蜱虫传播疾病

2021-11-23 “ E药世界”公众号 “ E药世界”公众号

蜱虫(Tick)是一种传播人兽共患病的重要媒介。作为严格的吸血性节肢动物,蜱几乎可以叮咬陆地上所有的动物,且吸血时间长、吸血量大、生活史复杂。

蜱虫(Tick)是一种传播人兽共患病的重要媒介。作为严格的吸血性节肢动物,蜱几乎可以叮咬陆地上所有的动物,且吸血时间长、吸血量大、生活史复杂。这些特点使蜱携带了最广泛的病原体种类,包括病毒、细菌、真菌、寄生虫;传播40余种疾病,如莱姆病、森林脑炎、克里米亚-刚果出血热、发热伴减少综合征、立克次体病、无形体病、巴贝西虫病等,可导致死亡或慢性后遗症,严重影响生活质量。

莱姆病,是伯氏疏螺旋体感染所致的自然疫源性疾病,通常是由黑腿蜱(I. scapularis)作为媒介传播。仅仅在美国,每年就有超过4万例莱姆病病例报告,而实际感染人数可能要高出十倍。莱姆病会损害神经系统,导致严重后果,其中一期莱姆病可以通过抗生素治疗,但如果发展到二期、三期,抗生素将无济于事,对神经系统造成的损伤将无法挽回。

新冠疫情大流行,让mRNA疫苗火速获批,随着mRNA新冠疫苗的大规模应用,让人们看到了mRNA疫苗的强大威力。因此,有研究人员开始研究mRNA疫苗在预防蜱传疾病中的预防潜力。

2021年11月17日,耶鲁大学医学院的研究人员在 Science 子刊 Science Translational Medicine 发表了题为:mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent 的研究论文,该论文还被选为当期的封面论文。

该研究没有针对特定的蜱传疾病病原体,而是针对蜱虫,用脂质纳米颗粒(LNP)递送在黑腿蜱的唾液中发现的19种蛋白(19ISP)的mRNA,促使皮肤对蜱虫叮咬产生快速反应,限制了蜱虫吸食血液和感染宿主的时间,还会让宿主能够快速发现蜱虫叮咬,从而预防黑腿蜱传播的莱姆病。

这种 mRNA 疫苗可在豚鼠体内提供保护,防止黑腿蜱叮咬引发的莱姆病感染,由于该疫苗是针对黑腿蜱,而非特定病原体,因此,还可以对抗其他蜱传疾病。

由于蜱虫携带了大量的病原体,因此蜱虫叮咬会造成多种疾病的传播,因此,研究团队没有针对特定的蜱虫传播的病原体,而是针对蜱虫开发疫苗。

耶鲁大学医学院的 Erol Fikrig 团队与 mRNA 疫苗奠基人、宾夕法尼亚大学的 Drew Weissman 团队合作,对传播莱姆病的黑腿蜱进行了研究,黑腿蜱的唾液中含有多种类型的蛋白质,研究团队将注意力放在了其中19种蛋白(19ISP)上。用产生这些蛋白质的 mRNA 片段作为疫苗的基础,这与在新冠 mRNA 疫苗中采取的策略相同。然后研究团队在豚鼠上测试这种 mRNA 疫苗的保护效果。因为豚鼠能够被蜱虫叮咬并感染莱姆病,因此,豚鼠常常被用作蜱传疾病研究模型。

与未接种 mRNA 疫苗的豚鼠相比,接种该疫苗的豚鼠被蜱虫叮咬的部位迅速发红,如果此时去除蜱虫,这些已接种的豚鼠都不会感染莱姆病,而有近50%的未接种豚鼠会感染。

当一个蜱虫叮咬而不被去除时,接种该疫苗的豚鼠都不会感染莱姆病,而60%的未接种豚鼠会感染。

当有三个蜱虫叮咬而不被去除时,该疫苗对豚鼠的保护作用会减弱,但接种该疫苗的豚鼠身上附着的蜱虫无法积极进食,且脱落的更快。

当一只蚊子叮咬你时,会立刻感觉到痛痒,从而提醒你赶走蚊子,但蜱虫叮咬时往往感觉不到,那是因为蜱虫分泌了麻醉皮肤的物质。

研究团队表示,这种 mRNA 疫苗不仅会让免疫系统识别蜱虫,从而防止感染莱姆病。而且,该疫苗会让蜱虫叮咬的部位迅速发红发痒,让蜱虫叮咬变得向蚊子叮咬一样被迅速发现,从而进一步帮助在传播病原体前将其去除。

研究团队表示,该 mRNA 疫苗可能比针对具体某一种病原体的疫苗提供更广泛的保护作用,而且,还能够与传统的基于病原体的疫苗联合使用,进一步提高保护力。

该论文的通讯作者 Erol Fikrig 表示,将进行更多研究以确定蜱虫唾液中的蛋白质可以用于预防蜱传疾病,最终还要进行人体实验确定该疫苗的功效。

原始出处:

ANDALEEB SAJID, et al. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. SCIENCE TRANSLATIONAL MEDICINE, 17 Nov 2021, Vol 13, Issue 620

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    2021-12-29 kalseyzl
  4. 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    2022-06-12 jeanqiuqiu
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  7. 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  8. 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    2021-11-24 jichang
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    2021-11-24 xfpan16
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