Cell子刊:新冠病毒25种“内部”蛋白质,或将成为疫苗新靶点

2022-06-28 转化医学网 网络

研究者表示,针对非规范抗原的抗体也许能在重症恢复中起到作用。

导读:随着Delta病毒和Omicron变体的出现,大多数的新冠疫苗和单克隆抗体已变得不再高效,因为刺突蛋白的突变帮助病毒逃过抗体的识别。而在病毒内部的蛋白质中,相关的积累突变却少很多。这意味着对这些“非规范性抗原”进行靶向,或将增强疫苗及新冠治疗的效果,使身体产生更强大的免疫力。近日,一项新研究为此进行了探索。

目前,不管是研究人体对SARS-CoV-2病毒的免疫力,还是探索新冠疫苗开发,刺突蛋白及其他病毒表面蛋白的抗体反应一直是研究者所关注的重点。但是,对于免疫力和疾病预后来说,能识别病毒内部蛋白质的抗体,也同等重要。近日,来自匹兹堡大学、佐治亚理工学院和埃默里大学的研究者完成的一项新研究支持了这个说法。

此项研究题为“Antibodies targeting conserved non-canonical antigens and endemic coronaviruses associate with favorable outcomes in severe COVID-19”,于6月12日发表于Cell Reports.

https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00809-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124722008099%3Fshowall%3Dtrue#secsectitle0045

研究者选取了21位新冠重症患者血清样本,进行了迄今为止最全面的COVID-19抗体分析。研究发现,在预测患者的生存率或死亡率方面,病毒内部蛋白的抗体谱(包括冠状病毒中存在的抗体谱)的预测效果和病毒表面蛋白的抗体谱的预测效果一样好。此发现或者表明,除了选择刺突蛋白进行靶向外,还可以对病毒的其他部分进行靶向;并且这种靶向将对新冠疫苗增强及新冠治疗影响重大。

“此项研究的新颖之处在于,我们对SARS-CoV-2病毒抗体做了深入的描绘,从不同的方面对抗体做了分析,” 该研究的共同资深作者Jishnu Das博士表示,“一直以来,人们一直关注刺突蛋白及受体结合域(receptor binding domain),但此研究提供了第一手详实证据,表明了针对病毒内蛋白的特异性抗体和重症新冠生存率之间,呈现正相关关系。”

当遇到病毒时,免疫系统会产生抗体,以帮助清理感染。每一种抗体仅识别一种抗原,这种抗原通常是一种病毒蛋白。大多数关于COVID-19免疫的研究,一直关注刺突蛋白及其他病毒表面蛋白(这些蛋白就像是病毒的外衣);然而,除了这些所谓的“规范抗原”外,SARS-CoV-2还具有25种病毒内部蛋白,也被该研究称作“非规范抗原”。

为了了解“非规范抗原”免疫反应是否能预测重症COVID-19患者的生存结果,此研究使用了一种微尺度抗体谱分析平台,对上述21位患者血清样本中的抗体做了全面分析,检测这些抗体对3种规范抗原、4种非规范抗原的免疫反应。此21名患者于2020年因患严重新冠住院(在疫苗获得批准之前),其中7位患者死亡,其他14人幸存。

该微尺度抗体谱分析平台对抗体的三个关键特点展开了分析。第一是抗体特异性,即抗体与什么物质进行绑定;第二是效应器功能,因为这影响着抗体在免疫反应中所扮演的角色;第三是糖基化,或可以理解为将碳水化合物分子添加到抗原中,这也会对抗体功能产生巨大影响。通过对此三个关键点的同时分析,研究者对于特定的抗体有了更深的了解,而不再仅仅局限于关注抗体滴度。

研究发现,关于此三个特点,没有一个特点可以单独解释患者生存结果;但从抗体谱的整体层面来分析时(不论是规范或非规范),幸存者和非幸存者之间存在明显的差异。这是一个具有重要意义的发现——和针对规范抗原的抗体一样,针对非规范抗原的抗体也同样能预测生存结果。研究者表示,针对非规范抗原的抗体也许能在重症恢复中起到作用。

随着Delta病毒和Omicron变体的出现,大多数的新冠疫苗和单克隆抗体(用于治疗新冠的人造抗体)已变得不再高效,因为刺突蛋白的突变帮助病毒免逃过抗体的识别。而在病毒内部的蛋白质中,相关的积累突变却少很多。这意味着对这些“非规范性抗原”进行靶向,或将增强疫苗及新冠治疗的效果,使身体产生更强大的免疫力,缓冲因病毒变异所带来的健康威胁。

上图:从患者样本中分离的严重感染SARS-CoV-2的病毒颗粒

在目前的工作中,研究团队正在利用抗体谱分析平台,对来自已接种疫苗人群和未接种疫苗人群的抗体做分析比对。随着时间的推移,不同抗体在预防新冠方面是否扮演着不同角色,这也是研究者所感兴趣的一个研究方向。

研究者还计划将他们的抗体谱分析平台扩展至其他领域,以研究不同抗体在其他方面的作用。例如,器官移植的排斥反应及其他传染性疾病。

参考资料:

https://medicalxpress.com/news/2022-06-spike-antibody-analysis-severe-covid-.html

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    2022-11-03 维他命
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    2022-06-29 lsndxfj
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该研究结果为将致病性抗COMP抗体与软骨结合提供了结构基础。识别的表位可以是瓜氨酸化的,RA患者中针对该表位的抗体水平升高并与较高的疾病活动度相关,这表明抗COMP抗体在部分RA患者中具有致病作用。

持续mepolizumab治疗能够让重度嗜酸性粒细胞性哮喘患者长期获益

持续mepolizumab治疗能够让重度嗜酸性粒细胞性哮喘患者获益,并支持血嗜酸性粒细胞作为mepolizumab治疗的生物标志物。

抗体通用名再也不叫“-mab”了,WHO出新规则了

2021年11月,WHO更新了抗体药通用名命名规则,距离2018年的修订已经过去了三年。

科普:抗体的概念与分类、结构

抗体,也叫免疫球蛋白 (Ig),是一种能特异性结合抗原的糖蛋白,而抗原是在易感染动物体内引发抗体产生的物质。在体内,抗体是由于外 源性分子的侵袭而产生的。抗体以一个或者多个 Y 字形单体存在,每个 Y

Lancet Respir Med:单克隆抗体adrecizumab对急性心源性休克患者的疗效

Adrecizumab在心源性休克患者中耐受性良好,但在第30天和第90天对心血管器官支持的需求并未减少,也未提高患者的生存率。