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Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
Nature ( IF 64.8 ) Pub Date : 2021-03-11 , DOI: 10.1038/s41586-021-03412-7
Dami A Collier 1, 2, 3 , Anna De Marco 4 , Isabella A T M Ferreira 1, 2 , Bo Meng 1, 2 , Rawlings P Datir 1, 2, 3 , Alexandra C Walls 5 , Steven A Kemp 1, 2, 3 , Jessica Bassi 4 , Dora Pinto 4 , Chiara Silacci-Fregni 4 , Siro Bianchi 4 , M Alejandra Tortorici 5 , John Bowen 5 , Katja Culap 4 , Stefano Jaconi 4 , Elisabetta Cameroni 4 , Gyorgy Snell 6 , Matteo S Pizzuto 4 , Alessandra Franzetti Pellanda 7 , Christian Garzoni 7 , Agostino Riva 8 , , Anne Elmer 9 , Nathalie Kingston 10 , Barbara Graves 10 , Laura E McCoy 3 , Kenneth G C Smith 1, 2 , John R Bradley 2, 10 , Nigel Temperton 11 , Lourdes Ceron-Gutierrez 12 , Gabriela Barcenas-Morales 12, 13 , , William Harvey 14 , Herbert W Virgin 6 , Antonio Lanzavecchia 4 , Luca Piccoli 4 , Rainer Doffinger 12, 15 , Mark Wills 2 , David Veesler 5 , Davide Corti 4 , Ravindra K Gupta 1, 2, 15, 16, 17, 18
Affiliation  

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.



中文翻译:

SARS-CoV-2 B.1.1.7 对 mRNA 疫苗引发抗体的敏感性

SARS-CoV-2 的传播在世界许多地方不受控制;由于 B.1.1.7 变种1的传播潜力较高,某些地区的控制变得更加复杂,目前已在 94 个国家/地区报告了这种情况。目前尚不清楚病毒对基于原型毒株的 SARS-CoV-2 疫苗的反应是否会受到 B.1.1.7 中发现的突变的影响。在这里,我们评估了接种基于 mRNA 的疫苗 BNT162b2 2后个体的免疫反应. 我们使用表达野生型刺突蛋白或包含 B.1.1.7 变体中发现的八个氨基酸变化的突变刺突蛋白的假病毒,测量了第一次和第二次免疫后的中和抗体反应。来自接受疫苗的个体的血清表现出广泛的针对野生型假病毒的中和效价,而针对 B.1.1.7 变体适度降低。这种减少在一些从 COVID-19 中康复的患者的血清中也很明显。对于靶向 N 末端结构域(10 个中的 9 个)和受体结合基序(31 个中的 5 个)的单克隆抗体,也观察到 B.1.1.7 变体的中和作用降低,但识别在受体结合基序之外结合的受体结合结构域。在 B.1.1.7 背景中引入编码 E484K 替换的突变以反映新出现的关注变体 (VOC 202102/02) 导致疫苗引发的抗体和单克隆抗体的中和活性更显着丧失( 31 个中的 19 个)与单独 B.1.1.7 中的突变所赋予的中和活性的丧失相比较。B.1.1.7 背景中 E484K 替代的出现代表了对 BNT162b2 疫苗功效的威胁。

更新日期:2021-03-11
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