Nat Commun:孙锟、饶子和共同研发出新型高亲和力,广谱新冠病毒中和抗体

2021-05-15 MedSci原创 MedSci原创

由上海交通大学医学院附属新华医院孙锟教授团队、协同南开大学饶子和院士团队、高诚生物、武汉病毒研究所等单位共同研发的一种新型新冠病毒中和抗体,在临床前研究中表现出对新冠病毒预防和治疗具有重要的作用,本项

由上海交通大学医学院附属新华医院孙锟教授团队、协同南开大学饶子和院士团队、高诚生物、武汉病毒研究所等单位共同研发的一种新型新冠病毒中和抗体,在临床前研究中表现出对新冠病毒预防和治疗具有重要的作用,本项研究结果发表在最新一期《自然—通讯》(Nature Communications)上。

虽然新冠疫苗可能预防大部分感染,但是,仍然有很多人群无法接种疫苗,或接种疫苗后,难以有效产生抗体,如儿童,高龄老年人,免疫功能低下,对疫苗严重过敏等。因此,仍然需要针对这类特殊人群开发具有针对性的治疗药物。

中和抗体与疫苗不同,就是一类针对病毒的高效治疗药物。它对于儿童、老年人,以及免疫功能低下的患者的新冠肺炎的治疗十分重要,可保护他们避免严重并发症,并改变儿童无防护的防治现状。

新型冠状病毒侵入人体,主要依赖刺突蛋白(Spike),他们就像一把把钥匙,能准确找到细胞的“钥匙孔”,使得病毒能进入细胞内部释放遗传信息,完成大量病毒复制,从而使人致病。因此,目前很多疫苗,中和抗体,均以针对Spike进行研发。有效的中和抗体能在钥匙齿痕“涂”上一层厚厚的“膜”,堵住了钥匙孔,使病毒无法进入细胞。

这一研究思路源于去年新冠疫情爆发的时候,新华医院儿科专家孙锟教授、感染科主任黄丽素第一时间就和单细胞测序技术顶尖的高诚生物讨论如何科学抗疫,考虑儿童防护的问题,他们将目标方向定在了中和抗体上。随后,借助于新冠患者康复期的血清,联合研究团队从上万个选择中,筛选出10个中和抗体,最终又从中选出新冠特异性中和抗体P4A1-2A。

Fig. 1: Characterization of neutralizing antibodies from convalescent patients.

figure1

进一步,联合研究团队还要将这一中和抗体“画像”,完成人工合成与开发。中国科学院院士、南开大学原校长饶子和院士通过结构生物学的深入研究发现新冠特异性中和抗体P4A1-2A如何作用于病毒。

中和抗体P4A1-2A有很多特色。首先是亲和力高,可以有效覆盖“钥匙齿痕”;其次是特别高效,低剂量单次注射即可显示高抗病毒活性,在恒河猴中,新冠病毒感染后单次注射中和抗体P4A1-2A即可完全清除病毒;再次是广谱,对目前检测的SARS-CoV-2变异型均显示中和活性,病毒逃逸和耐药可能性低;同时还可以打“持久战”,具有较长的半衰期,有望长期对抗新冠病毒感染;另外,还表现出较好的安全性,该抗体的I期临床试验中均具有良好的耐受性。

Therapeutic efficacy of in the rhesus macaque model of SARS-CoV-2 infection.

figure4

“我们希望这一中和抗体能很快使患者受益,包括那些不能从疫苗中受益或不能接种疫苗的患者,如幼儿、老年人和某些免疫功能低下人群。”孙锟指出,“像P4A1-2A这样的中和抗体,不仅可以保护这些特殊人群避免严重并发症,还有望抑制新冠病毒的传播。我们还设想将该抗体可应用于应急保护。 ”

“从康复病人体内分离并开发的单克隆抗体,或是对抗新冠病毒感染最有效的武器之一。这是目前国内外诸多研究机构的重点关注方向,新华医院共同参与的此次研发项目,整体进度走在前列。” 该论文的共同通讯作者、上海交通大学医学院附属新华医院院长孙锟教授说,“很高兴地看到医生在临床研究中的工作,能够与基础研究团队、交叉转化团队高效合作和推进,才能迅速地对这抗体进行改造和开发,并推向临床。”

目前,该中和抗体目前已经进入药物临床试验中。

原始出处:

Guo Y, Huang L, Zhang G, Yao Y, Zhou H, Shen S, Shen B, Li B, Li X, Zhang Q, Chen M, Chen D, Wu J, Fu D, Zeng X, Feng M, Pi C, Wang Y, Zhou X, Lu M, Li Y, Fang Y, Lu YY, Hu X, Wang S, Zhang W, Gao G, Adrian F, Wang Q, Yu F, Peng Y, Gabibov AG, Min J, Wang Y, Huang H, Stepanov A, Zhang W, Cai Y, Liu J, Yuan Z, Zhang C, Lou Z, Deng F, Zhang H, Shan C, Schweizer L, Sun K, Rao Z. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.Nat Commun. 2021 May 11;12(1):2623. doi: 10.1038/s41467-021-22926-2

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    2022-02-24 liuli5079
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    2021-08-02 liye789132251
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    2021-05-17 lqvr
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    2021-05-16 一叶,一菩提

    哇,期待

    0

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    2021-05-15 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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