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SARS-CoV-2 B.1.1.7 对 mRNA 疫苗诱导抗体的敏感性。

Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies.

机构信息

Cambridge Institute of Therapeutic Immunology & Infectious Disease, Cambridge, UK.

Department of Medicine, University of Cambridge, Cambridge, UK.

出版信息

Nature. 2021 May;593(7857):136-141. doi: 10.1038/s41586-021-03412-7. Epub 2021 Mar 11.

Abstract

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 variant, 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 BNT162b2. 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.

摘要

在世界许多地区,SARS-CoV-2 的传播仍未得到控制;在某些地区,B.1.1.7 变体的更高传播能力使情况更加复杂,该变体现已在 94 个国家报告。目前尚不清楚病毒对基于 SARS-CoV-2 原型株的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,我们评估了基于 mRNA 的疫苗 BNT162b2 接种后的个体免疫反应。我们使用表达野生型刺突蛋白或含有 B.1.1.7 变体中发现的 8 个氨基酸变化的突变刺突蛋白的假病毒来测量首次和第二次免疫后的中和抗体反应。接种疫苗的个体的血清显示出针对野生型假病毒的广泛中和效价范围,针对 B.1.1.7 变体的中和效价略有降低。在一些从 COVID-19 中康复的患者的血清中也观察到了这种降低。针对靶向 N 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对 B.1.1.7 变体的中和作用降低,但识别受体结合域的单克隆抗体不会中和作用降低,该受体结合域位于受体结合基序之外。在 B.1.1.7 背景下引入编码 E484K 取代的突变以反映新出现的关注变体(VOC 202102/02),与 B.1.1.7 突变单独引起的中和活性丧失相比,疫苗诱导的抗体和单克隆抗体的中和活性损失更大(31 个中的 19 个)。E484K 取代在 B.1.1.7 背景下的出现对 BNT162b2 疫苗的功效构成威胁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9121/7616976/143b1f0c5e23/EMS143798-f005.jpg

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