Nature Communications:羊驼拯救世界?科学家发现,理想的COVID-19疫苗可能来自这一“神兽”

2021-09-25 生物探索 生物探索

研究人员研发出4款源自美洲驼的独特纳米抗体,具有预防COVID-19的潜力。在小鼠试验中,其中一款疫苗不仅可注射使用,而且通过鼻腔吸入这一途径同样展现出良好的预防效果。

针对由新型冠状病毒(SARS-CoV-2)引发的新冠肺炎(COVID-19),当前全球已有多款疫苗上市。然而,尽管各大制造商均在全力生产疫苗,接种的速度仍然赶不上人们的需求,与此同时,随着变异毒株的不断出现,疫苗的效力开始下降。研制出一款产量更大、效果更持久的COVID-19疫苗成为科学家们正在探索的目标。

当地时间9月22日,英国牛津大学威康人类遗传学中心的研究人员领衔在《Nature Communications》上发表了一篇题为“A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacyin the Syrian golden hamster model of COVID-19”的研究报告。

在这项报告中,研究人员研发出4款源自美洲驼的独特纳米抗体,具有预防COVID-19的潜力。在小鼠试验中,其中一款疫苗不仅可注射使用,而且通过鼻腔吸入这一途径同样展现出良好的预防效果。

与传统抗体相比,纳米抗体具有多种优势,比如分子尺寸小、稳定性高的特点使其能够通过雾化方式直接实现局部给药,提高疫苗的生物利用度提高和治疗依从性,另外技术的进步使得制造纳米抗体的成本更低。基于这些因素,研究人员探索了使用纳米抗体抗击COVID-19的潜力。

如何制造纳米抗体呢?研究人员将目光放在了美洲驼,也就是大羊驼身上。通过将SARS-CoV-2 刺突蛋白注射到美洲驼体内,触发其免疫反应,从而得到一系列单域重链抗体(VHH)。

研究人员从中筛选出C1、H3、C5以及F2这4种对病毒S蛋白的受体结合区域(RBD)具有最高亲和力的 VHH进行生产,并通过表面等离子体共振 (SPR) 测量联合竞争结合试验中,评估了每种VHH与Alpha、Beta等新冠毒株的 RBD 体外结合效果。试验结果表明,H3、C5以及F2能够有效中和SARS-CoV-2原始毒株以及Alpha 变异株,而对 Beta变异株具有活性的纳米抗体仅有C1。

由于C5在体外整体表现最佳,因此研究人员选择了这一纳米抗体进行了进一步研究。通过给6只感染SARS-CoV-2后与人体症状相似的叙利亚仓鼠模型腹膜注射C5纳米抗体,研究人员发现,这款纳米抗体能够让受感染的小鼠疾病症状显着减轻,并且7天后体重减轻的程度远低于未接受纳米抗体治疗的仓鼠。另外,与对照组相比,接受纳米抗体治疗的仓鼠在 7 天后肺部和呼吸道的病毒载量也较低。

C5纳米抗体腹腔注射后对叙利亚仓鼠的治疗效果

在随后的研究中,研究人员还发现,不仅仅是注射给药,即使是呼吸给药的途径也能够充分发挥出C5纳米抗体的效果。

该报告的通讯作者之一、英国牛津大学威康人类遗传学中心结构生物学部教授James H. Naismith说:“如果我们的这款疫苗最终研制成功并获得批准上市,那么纳米抗体将能够在世界范围内提供重要COVID-19的治疗方法,因为它们比人类抗体更容易生产,并且不需要储存在冷藏设施中。”

总之,这项研究为 COVID-19 提供了一种重要的新治疗形式,表明源自羊驼的纳米抗体可能是帮助人们抗击疫情的重要力量,值得注意的是,不仅仅是预防和治疗COVID0-19,在这项试验中,研究人员研制纳米抗体的技术或许也将在今后帮助人们尽快开发出必要的疗法。

原始出处:

Huo, J., Mikolajek, H., Le Bas, A. et al. A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19. Nat Commun 12, 5469 (2021). https://doi.org/10.1038/s41467-021-25480-z.

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    2022-03-03 liuli5079
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    2021-11-30 liye789132251
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    2021-09-26 病毒猎手

    #羊驼#绝对是神兽,能直接产生#纳米抗体#。在羊驼外周血液中存在一种天然缺失轻链的抗体,该抗体只包含一个重链可变区(VHH)和两个常规的CH2与CH3区,但却不像人工改造的单链抗体片段 (scFv) 那样容易相互沾粘,甚至聚集成块。更重要的是单独克隆并表达出来的VHH结构具有与原重链抗体相当的结构稳定性以及与抗原的结合活性,是已知的可结合目标抗原的最小单位。VHH晶体为2.5nm,长4nm,分子量只有15KDa,此也被称作纳米抗体(Nanobody, Nb)

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