Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
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DOI:
10.1038/s41591-021-01318-5
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发表时间:
2021-03-26
期刊:
影响因子:
82.9
通讯作者:
Schwartz, Olivier
Schwartz, Olivier
中科院分区:
医学1区
文献类型:
--
作者:
Planas, Delphine;Bruel, Timothee;Schwartz, Olivier

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2019年冠状病毒病恢复期患者和接种BNT162b2疫苗的患者的血清中和SARS-CoV-2变种B1.1.7和B.1.351的能力降低,但在接种两剂疫苗后,针对这些变种的抗体效力提高。几种急性呼吸综合征冠状病毒(SARS-CoV-2)B.1.1.7和B.1.351变种分别在英国和南非被首次发现,并已蔓延到许多国家。这些变异体在编码尖峰蛋白的基因上存在不同的突变,这引起了人们对它们免疫逃避潜力的重要担忧。在这里,我们从急性感染的个体中分离出传染性B.1.1.7和B.1.351菌株。我们检测了这两种变异体对血清和鼻拭子中存在的SARS-CoV-2抗体的敏感性,这些抗体来自以前感染过流行毒株或最近接种过疫苗的人,并与D614G参考病毒进行了比较。我们使用了一种新的快速中和试验,基于过夜感染后呈GFP阳性的报告细胞。来自58名恢复期患者的血清在症状出现后9个月内收集,同样中和了B.1.1.7和D614G。相比之下,9个月后,恢复期血清中和效价平均下降了6倍,40%的样本缺乏任何抗B.1.351的活性。与D614G相比,19名接种了两次辉瑞Cominarty的人的血清在接种后6周进行了纵向测试,与D614G相比,对B.1.1.7的效力相同,但对B.1.351的效力较低。中和效价在第二次疫苗接种后有所增加,但对B.1.351疫苗的中和效价仍低14倍。相比之下,恢复期或接种疫苗的人的血清在基于流式细胞术的血清学分析中类似地结合了这三种尖峰蛋白。在接种者的鼻拭子中很少检测到中和抗体。因此,传播更快的SARS-CoV-2变种对自然感染或疫苗接种产生的中和抗体产生部分抵抗力,这在抗体水平较低的个人中最常见。我们的结果表明,B1.351而不是B.1.1.7可能会增加免疫个体的感染风险。
Sera from convalescent individuals with coronavirus disease 2019 and from individuals vaccinated with BNT162b2 have reduced ability to neutralize SARS-CoV-2 variants B1.1.7 and B.1.351, but antibody potency against the variants increases after two vaccine doses.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.