University of Chicagogrid.170205.1 Department of Medicine, Section of Rheumatology, Chicago, Illinois, USA.
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
mBio. 2021 Dec 21;12(6):e0297521. doi: 10.1128/mBio.02975-21. Epub 2021 Nov 16.
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.
多种严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变异株已经出现，这些变异株表现出更高的病毒传播能力，并部分逃避了自然感染和疫苗接种所诱导的免疫。为了确定受近期病毒变异株影响的特定抗体靶标，我们从 10 位恢复期供体中产生了 43 种单克隆抗体（mAbs），这些 mAbs 结合了 SARS-CoV-2 刺突的三个不同结构域。携带 K417、E484 和 N501 突变的病毒变异株可以逃避针对受体结合域（RBD）的大多数高效抗体。尽管如此，我们还是鉴定出了 12 种针对刺突蛋白三个不同区域的中和 mAbs，这些 mAbs可以中和 SARS-CoV-2 和关注变异株（VOCs），包括 B.1.1.7（alpha）、P.1（gamma）和 B.1.617.2（delta）。值得注意的是，针对不同表位的抗体可以中和不同的变异株，这表明不同的变异株可能已经进化到可以破坏特定中和抗体类别的结合。这些结果强调，暴露于原型 SARS-CoV-2 第一次大流行的人类具有针对当前变异株的中和抗体，诱导针对刺突多个不同表位的中和抗体以中和新兴的关注变异株至关重要。 我们描述了一组来自 10 位 2019 年冠状病毒病（COVID-19）恢复期供体的记忆 B 细胞的新型人源单克隆抗体针对原型 SARS-CoV-2 第一次大流行中病毒的结合和中和特性。有 12 种针对刺突上不同表位的抗体，包括 RBD 上的两个位点和 N 端结构域（NTD）上的一个位点，这些抗体显示对 VOCs 的交叉中和作用，针对不同的抗体靶标可以中和不同的变异株。这项工作强调了 SARS-CoV-2 的自然感染仅能引起针对某些 VOCs 的有效交叉中和作用，并支持 COVID-19 疫苗接种的必要性，以有效地诱导针对刺突蛋白多个表位的中和抗体，以对抗当前的 SARS-CoV-2 VOCs 和未来可能出现的任何其他变异株。
N Engl J Med. 2021-8-12
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