Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects.

Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects.
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DOI:
10.1016/j.celrep.2021.109353
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发表时间:
2021-07-13
期刊:
影响因子:
8.8
通讯作者:
Stamatatos L
Stamatatos L
中科院分区:
生物学1区
文献类型:
--
作者:
Jennewein MF;MacCamy AJ;Akins NR;Feng J;Homad LJ;Hurlburt NK;Seydoux E;Wan YH;Stuart AB;Edara VV;Floyd K;Vanderheiden A;Mascola JR;Doria-Rose N;Wang L;Yang ES;Chu HY;Torres JL;Ozorowski G;Ward AB;Whaley RE;Cohen KW;Pancera M;McElrath MJ;Englund JA;Finzi A;Suthar MS;McGuire AT;Stamatatos L

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SARS-CoV-2是过去20年中跨越动物到人类屏障并引起广泛疾病的三种冠状病毒之一。开发一种通用的人类冠状病毒疫苗可以预防未来的大流行。我们表征了从4名COVID-19+受试者中分离的198种抗体,并鉴定了14种SARS-CoV-2中和抗体。一个靶向N-末端结构域(NTD),一个识别S2中的表位,11个结合受体结合结构域(RBD)。三种抗RBD中和抗体通过有效阻断SARS-CoV-1和SARS-CoV-2 RBD与ACE 2受体的结合来交叉中和SARS-CoV-1。使用K18-hACE转基因小鼠模型,我们证明中和效力和抗体表位特异性调节抗SARS-CoV-2抗体的体内保护潜力。所有四种交叉中和抗体均中和B.1.351突变株。因此,我们的研究表明,S2中的表位可以作为设计能够引发交叉中和冠状病毒抗体的免疫原的蓝图。从4名患者中分离的14种抗SARS-CoV-2中和mAb中,3种抗RBD和1种抗S2 mAb中和SARS-CoV-1和B.1.351变体小鼠研究显示抗NTD mAb的潜在保护作用。从4名患者中分离出14种抗SARS-CoV-2中和抗体,其中1种抗S2,1种抗NTD,11种抗RBD。三种抗RBD和抗S2 nAb交叉中和SARS-CoV-1和B.1.351。抗NTD mAb在小鼠中赋予部分保护作用。进化的抗S2抗体可能为泛冠状病毒疫苗提供模板。
SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies. Fourteen anti-SARS-CoV-2 neutralizing mAbs isolated from four patients Three anti-RBD and one anti-S2 mAb neutralized SARS-CoV-1 and the B.1.351 variant Mouse studies show potential protective effect of anti-NTD mAbs Jennewein et al. isolated 14 anti-SARS-CoV-2 neutralizing antibodies—one anti-S2, one anti-NTD, and 11 anti-RBD—from four patients. Three anti-RBD and the anti-S2 nAbs cross-neutralized SARS-CoV-1 and B.1.351. The anti-NTD mAbs conferred partial protection in mice. Evolved anti-S2 Abs may provide templates for pan-coronavirus vaccines.
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