Antibodies induced by an ancestral SARS-CoV-2 strain that cross-neutralize variants from Alpha to Omicron BA.1.
Antibodies induced by an ancestral SARS-CoV-2 strain that cross-neutralize variants from Alpha to Omicron BA.1.
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DOI：
10.1126/sciimmunol.abo3425
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发表时间：
2022-08-12
影响因子：
24.8
通讯作者：
中科院分区：
文献类型：
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作者：
识别SARS-CoV-2刺突糖蛋白的中和抗体是抵抗病毒入侵的主要宿主防御。SARS-CoV-2的变体携带突变，允许逃避许多抗体的中和，特别是那些属于广泛分布在人群中的类别的抗体。识别中和这些令人担忧的变体的抗体并确定其患病率是了解免疫保护的重要目标。为了确定由初始武汉毒株感染建立的B细胞库的Delta和Omicron BA.1变体特异性，我们测量了来自早期记忆B细胞应答的无偏调查的73种抗体的中和效力。识别刺突受体结合结构域（RBD）上三个先前定义的表位区域中的每一个的抗体在中和效力和变体逃逸抗性方面各不相同。ACE 2结合表面（“RBD-2”）具有最高效力但对病毒逃逸具有最大敏感性的中和抗体的结合位点; RBD上的两个其他表位区域（“RBD-1和“RBD-3”）结合效力更适中但宽度更大的抗体。中和所有五种测试的相关变体的几种Fab B：刺突复合物的结构，包括来自RBD-1、RBD-2和RBD-3簇的各一种Fab B，说明了广泛中和的决定因素，并显示B细胞库可具有避免由广泛分布的（“公共”）抗体驱动的免疫逃逸的特异性。RBD-2结合的广泛中和剂的结构显示了为什么它保留了Omicron BA.1的中和活性，而不像同一公共类中的大多数其他中和剂。我们的研究结果与疫苗有效性的真实数据相关，这表明Omicron BA.1引起的疾病有所缓解。来自武汉株感染的SARS-CoV-2刺突结合抗体的结构显示出中和所关注变体所需的特征。
Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many antibodies, especially those belonging to classes widely distributed in the human population. Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection. To determine the Delta- and Omicron BA.1-variant specificity of B cell repertoires established by an initial Wuhan strain infection, we measured neutralization potencies of 73 antibodies from an unbiased survey of the early memory B cell response. Antibodies recognizing each of three, previously defined, epitopic regions on the spike receptor-binding domain (RBD) varied in neutralization potency and variant-escape resistance. The ACE2 binding surface (“RBD-2”) harbored the binding sites of the neutralizing antibodies with highest potency but with the greatest sensitivity to viral escape; two other epitopic regions on the RBD (“RBD-1 and “RBD-3”) bound antibodies of more modest potency but greater breadth. The structures of several Fab:spike complexes that neutralized all five variants of concern tested, including one Fab each from the RBD-1, -2 and -3 clusters, illustrated the determinants of broad neutralization and showed that B cell repertoires can have specificities that avoid immune escape driven by widely distributed (“public”) antibodies. The structure of the RBD-2-binding, broad neutralizer shows why it retains neutralizing activity for Omicron BA.1, unlike most others in the same public class. Our results correlate with real-world data on vaccine efficacy, which indicate mitigation of disease caused by Omicron BA.1. Structures of SARS-CoV-2 spike-bound antibodies from Wuhan-strain infection show features needed to neutralize variants of concern.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
两种抗体鸡尾酒中和中和的遗传和结构基础。
影响因子：
28.3
作者：
Dong J;Zost SJ;Greaney AJ;Starr TN;Dingens AS;Chen EC;Chen RE;Case JB;Sutton RE;Gilchuk P;Rodriguez J;Armstrong E;Gainza C;Nargi RS;Binshtein E;Xie X;Zhang X;Shi PY;Logue J;Weston S;McGrath ME;Frieman MB;Brady T;Tuffy KM;Bright H;Loo YM;McTamney PM;Esser MT;Carnahan RH;Diamond MS;Bloom JD;Crowe JE Jr
通讯作者：
Crowe JE Jr
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
5.4
作者：
Johnson MC;Lyddon TD;Suarez R;Salcedo B;LePique M;Graham M;Ricana C;Robinson C;Ritter DG
通讯作者：
Ritter DG