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新冠康复患者血浆中的刺突蛋白蛋白酶抗体有助于中和 SARS-CoV-2。

Spike-protein proteolytic antibodies in COVID-19 convalescent plasma contribute to SARS-CoV-2 neutralization.

机构信息

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.

出版信息

Cell Chem Biol. 2023 Jul 20;30(7):726-738.e4. doi: 10.1016/j.chembiol.2023.05.011. Epub 2023 Jun 23.

DOI:10.1016/j.chembiol.2023.05.011
PMID:37354908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10288624/
Abstract

Understanding the mechanisms of antibody-mediated neutralization of SARS-CoV-2 is critical in combating the COVID-19 pandemic. Based on previous reports of antibody catalysis, we investigated the proteolysis of spike (S) by antibodies in COVID-19 convalescent plasma (CCP) and its contribution to viral neutralization. Quenched fluorescent peptides were designed based on S epitopes to sensitively detect antibody-mediated proteolysis. We observed epitope cleavage by CCP from different donors which persisted when plasma was heat-treated or when IgG was isolated from plasma. Further, purified CCP antibodies proteolyzed recombinant S domains, as well as authentic viral S. Cleavage of S variants suggests CCP antibody-mediated proteolysis is a durable phenomenon despite antigenic drift. We differentiated viral neutralization occurring via direct interference with receptor binding from that occurring by antibody-mediated proteolysis, demonstrating that antibody catalysis enhanced neutralization. These results suggest that antibody-catalyzed damage of S is an immunologically relevant function of neutralizing antibodies against SARS-CoV-2.

摘要

了解抗体介导的 SARS-CoV-2 中和机制对于抗击 COVID-19 大流行至关重要。基于先前关于抗体催化的报告，我们研究了 COVID-19 恢复期血浆 (CCP) 中抗体对刺突 (S) 的蛋白水解作用及其对病毒中和的贡献。根据 S 表位设计了猝灭荧光肽，以灵敏地检测抗体介导的蛋白水解。我们观察到来自不同供体的 CCP 中的表位切割，当血浆进行热处理或 IgG 从血浆中分离时，这种切割仍然存在。此外，纯化的 CCP 抗体可蛋白水解重组 S 结构域和真实病毒 S。S 变体的切割表明，尽管抗原漂移，CCP 抗体介导的蛋白水解仍然是一种持久现象。我们区分了通过直接干扰受体结合而发生的病毒中和与通过抗体介导的蛋白水解而发生的中和，证明抗体催化增强了中和作用。这些结果表明，S 的抗体催化损伤是针对 SARS-CoV-2 的中和抗体的一种具有免疫相关性的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/dd1dca2a5c1d/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/f716b18f99dd/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/abc72a624d3c/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/12b82171984e/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/97b7675711f0/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/be6b52ac2420/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/5bac0b8f4f3e/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/fd7b66e7875e/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/dd1dca2a5c1d/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/f716b18f99dd/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/abc72a624d3c/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/12b82171984e/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/97b7675711f0/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/be6b52ac2420/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/5bac0b8f4f3e/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/fd7b66e7875e/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea24/10288624/dd1dca2a5c1d/gr7_lrg.jpg

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