Rapid characterization of spike variants via mammalian cell surface display.
Rapid characterization of spike variants via mammalian cell surface display.
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通过哺乳动物细胞表面显示快速表征尖峰变异。
DOI：
10.1016/j.molcel.2021.11.024
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发表时间：
2021-12-16
期刊：
影响因子：
16
通讯作者：
Finkelstein IJ
中科院分区：
文献类型：
--
作者：
Javanmardi K;Chou CW;Terrace CI;Annapareddy A;Kaoud TS;Guo Q;Lutgens J;Zorkic H;Horton AP;Gardner EC;Nguyen G;Boutz DR;Goike J;Voss WN;Kuo HC;Dalby KN;Gollihar JD;Finkelstein IJ
SARS-CoV-2刺突蛋白是疫苗的关键成分，也是中和单克隆抗体（nAb）的靶点。刺突也正在进行免疫原性选择与变异，增加感染性和部分逃脱恢复期血浆。在这里，我们描述了Spike Display，这是一种高通量平台，可快速表征多种冠状病毒家族蛋白中的糖基化刺突胞外域。我们分析了1000种变异SARS-CoV-2刺突的表达、ACE 2结合和13种nAb的识别。所有五个N-末端结构域（NTD）环的丙氨酸扫描突出显示了N1，N3和N5环中被大多数NTD结合nAb识别的公共表位。关注的变体B.1.1.7（alpha）、B.1.351（beta）、B.1.1.28（gamma）、B.1.427/B.1.429（delta）和B.1.617.2（delta）中的NTD突变影响尖峰表达并逃避大多数NTD靶向nAb。最后，B.1.351和B.1.1.28完全逃脱了强效ACE 2模拟物。我们预计Spike Display将加速SARS-CoV-2和其他新兴病毒威胁的抗原设计，深度扫描诱变和抗体表位定位。Spike Display加速了SARS-CoV-2刺突蛋白的基因型-表型研究N-末端结构域环N1、N3和N5形成了中和抗体的公共表位令人担忧的变体逃避了几类NTD靶向中和抗体ACE 2肽模拟物已经失去了对几种广泛传播的变体的效力SARS-CoV-2刺突蛋白是免疫系统的关键靶标。Javanmarti等人报道了一种用于快速筛选刺突变体的抗原性和ACE 2亲和力的哺乳动物细胞展示平台。该平台称为Spike Display，可加速病毒糖蛋白的抗原设计和抗体表位定位。
The SARS-CoV-2 spike protein is a critical component of vaccines and a target for neutralizing monoclonal antibodies (nAbs). Spike is also undergoing immunogenic selection with variants that increase infectivity and partially escape convalescent plasma. Here, we describe Spike Display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ∼200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by 13 nAbs. An alanine scan of all five N-terminal domain (NTD) loops highlights a public epitope in the N1, N3, and N5 loops recognized by most NTD-binding nAbs. NTD mutations in variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.1.28 (gamma), B.1.427/B.1.429 (epsilon), and B.1.617.2 (delta) impact spike expression and escape most NTD-targeting nAbs. Finally, B.1.351 and B.1.1.28 completely escape a potent ACE2 mimic. We anticipate that Spike Display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats. Spike Display accelerates genotype-to-phenotype studies of SARS-CoV-2 spike protein N-terminal domain loops N1, N3, and N5 form a public epitope for neutralizing antibodies Variants of concern escape several classes of NTD-targeting neutralizing antibodies An ACE2 peptide mimic has lost potency against several broadly circulating variants The SARS-CoV-2 spike protein is a critical target of the immune system. Javanmardi et al. report a mammalian cell display platform for rapidly screening the antigenicity and ACE2 affinity of spike variants. This platform, termed Spike Display, accelerates antigen design and antibody epitope mapping for viral glycoproteins.
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影响因子：
16.6
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
通讯作者：
Bloom JD
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
56.9
作者：
Hamilton, SR;Bobrowicz, P;Gerngross, TU
通讯作者：
Gerngross, TU
影响因子：
3
作者：
Daily J
通讯作者：
Daily J