bioRxiv:应对全球新冠病毒变种,防御南非变种已成为重中之重!

2021-03-24 MedSci原创 MedSci原创

现有疫苗诱导的抗体仍可以中和巴西冠状病毒P.1变体,但水平较低。

近日,牛津大学科学家在bioRxiv发布,现有疫苗诱导的抗体仍可以中和巴西冠状病毒P.1变体,但水平较低。P.1对自然获得的或疫苗诱导的抗体应答明显低于南非B.1.351变种,这表明靶向受体结合域(RBD)之外的变化会影响中和作用。

目前,全球正在大规模的疫苗接种,这些疫苗的产生源自早期分离的病毒毒株,但随着疫情的规模的流行,出现了具有多个突变的新菌株:来自巴西的P.1变种,来自南非的B.1.351变种和来自英国的B.1.1.7变种。所有这些都在ACE2结合位点发生突变,其中P.1B.1.351具有几乎相同的突变体:E484KK417TN501Y,均对ACE2具有相似的亲和力。

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研究人员对202012月从巴西马瑙斯的一名感染患者的咽拭子中分离的P.1变体进行培养,并通过接种阿斯利康或辉瑞/BioNTech疫苗来中和P.1变体。结果显示,疫苗产生的抗体对B.1.1.7P.1变体中和降低了近3倍,而对于南非的B.1.351变体降低了7.6倍。

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P.1被单克隆抗体中和情况

南非B.1.351变体的发现更令人担忧,因为这种变体不仅难于被大多数NTD单克隆抗体所中和,而且难以被RBD上受体结合基序的多个单个单克隆抗体所中和,这在很大程度上是由于E484K突变所致。此外,B.1.351对恢复性血浆和疫苗后血清的中和作用具有明显的抗性。

317日,发表在NEJM上的一项研究报告称,阿斯利康疫苗对南非B.1.351变种COVID-19变种无效。该研究对南非1467名患者进行了评估,发现在接种疫苗人群中,有19人(占2.5%)在接受第二剂疫苗后至少14天出现轻度至中度COVID-19,而接受安慰剂的人群中有23人(占3.2%)。在42名感染的患者中,39名来自B.1.351南非变种,该研究推算对该变种的有效性为10.9%

伪病毒和活病毒中和测定结果

研究人员表示,由于P.1B.1.351在受体结合结构域中具有非常相似的变化,我们可以假设中和抗体会受到类似的影响,针对B.1.351的轻度至中度疾病的疫苗效力下降可能反映了受体结合域之外发生的突变。”

“B.1.351和具有相似突刺突变的新兴变体对单克隆抗体治疗提出了新的挑战,并威胁到当前疫苗的保护功效。开发B.1.351的疫苗应该是全球疫苗开发人员的首要任务研究人员进一步强调到。

目前,防御南非变种!Moderna的变异特异性COVID-19候选疫苗即将进入临床阶段。还计划评估另外两种增强免疫力的方法,以增强抵抗SARS-CoV-2突变的免疫力。包括被称为mRNA-1273.211的多价加强免疫候选物,它将在50 mcg或更低剂量中联合mRNA-1273mRNA-1273.351

除了这种加强策略外,该公司还表示计划在血清阴性个体中使用mRNA-1273.351mRNA-1273.211作为针对COVID-19的主要疫苗,将以100 mcg或更低的剂量施用两种剂量的方案。

参考资料

1Wanwisa Dejnirattisai, et al.Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2.doi: https://doi.org/10.1101/2021.03.12.435194

2,Shabir A. Madhi, Ph.D., Vicky Baillie, Ph.D., Clare L. Cutland, Ph.D.Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.DOI: 10.1056/NEJMoa2102214

3https://www.nature.com/articles/s41586-021-03398-2_reference.pdf

4Neutralizing Activity of BNT162b2-Elicited Serumhttps://www.nejm.org/doi/full/10.1056/NEJMc2102017?query=featured_home

5https://www.firstwordpharma.com/node/1803892?tsid=4

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    2021-05-18 sunylz
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    2021-03-24 志明

    这场疫情要影响多久?3年?5年?

    0

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    2021-03-26 hongbochen
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    2021-03-24 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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