Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.
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靶向茎螺旋的罕见，收敛的抗体广泛中和多种贝塔曲霉病毒。
DOI：
10.1016/j.chom.2022.10.010
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发表时间：
2023-01-11
影响因子：
30.3
通讯作者：
Tan, Joshua
中科院分区：
文献类型：
--
作者：
Dacon, Cherrelle;Peng, Linghang;Lin, Ting-Hui;Tucker, Courtney;Lee, Chang-Chun D.;Cong, Yu;Wang, Lingshu;Purser, Lauren;Cooper, Andrew J. R.;Williams, Jazmean K.;Pyo, Chul-Woo;Yuan, Meng;Kosik, Ivan;Hu, Zhe;Zhao, Ming;Mohan, Divya;Peterson, Mary;Skinner, Jeff;Dixit, Saurabh;Kollins, Erin;Huzella, Louis;Perry, Donna;Byrum, Russell;Lembirik, Sanae;Murphy, Michael;Zhang, Yi;Yang, Eun Sung;Chen, Man;Leung, Kwanyee;Weinberg, Rona S.;Pegu, Amarendra;Geraghty, Daniel E.;Davidson, Edgar;Doranz, Benjamin J.;Douagi, Iyadh;Moir, Susan;Yewdell, Jonathan W.;Schmaljohn, Connie;Crompton, Peter D.;Mascola, John R.;Holbrook, Michael R.;Nemazee, David;Wilson, Ian A.;Tan, Joshua
人类最近面临着三次新型贝塔冠状病毒的爆发，强调需要开发出广泛针对冠状病毒的方法。在这里，我们从新冠肺炎康复期捐赠者中鉴定出55种与不同的贝塔冠状病毒刺突蛋白结合的单抗。大多数抗体针对的是包含K814残基的S2表位，并且是非中和的。然而，11种针对茎螺旋的抗体中和了来自不同谱系的贝塔冠状病毒。这一组中的8种抗体，包括6种最广泛和最有效的中和剂，由IGHV1-46和IGKV3-20编码。这类抗体的晶体结构在1.5-1.75？分辨率下显示了保守的结合模式。COV89-22中和了令人担忧的SARS-CoV-2变种，包括Omicron BA.4/5和叙利亚仓鼠的有限疾病。总的来说，这些发现确定了一类IGHV1-46/IGKV3-20抗体，它们通过靶向茎螺旋来广泛中和贝塔冠状病毒，但表明这些抗体构成了感染SARS-CoV-2后对贝塔冠状病毒的广泛反应的抗体反应的一小部分。分离出55株广泛反应的抗β冠状病毒的单抗只有少数是广泛中和的，并以茎螺旋为靶标鉴定IGHV1-46/IGKV3-20基因的广泛中和物的特征IGHV1-46/IGKV3-20抗体的广泛中和物结构揭示了一种保守的结合模式，而广泛中和冠状病毒的抗体的特征尚不清楚。在这里，Dacon等人。从新冠肺炎康复期捐赠者中鉴定一类针对茎螺旋的单抗，它能中和多种贝塔冠状病毒，使用IGHF1-46/IGKV3-20基因签名，并以保守的方式与Spike蛋白结合。
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5–1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection. Isolation of 55 broadly reactive monoclonal antibodies to betacoronaviruses Only a minority are broadly neutralizing and target the stem helix Identification of an IGHV1-46/IGKV3-20 gene signature of the broad neutralizers Structures of IGHV1-46/IGKV3-20 antibodies reveal a conserved mode of binding The characteristics of antibodies that broadly neutralize coronaviruses are poorly understood. Here, Dacon et al. identify a class of stem helix-specific monoclonal antibodies from COVID-19 convalescent donors that neutralize diverse betacoronaviruses, use an IGHV1-46/IGKV3-20 gene signature, and bind in a conserved manner to the spike protein.
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影响因子：
6.1
作者：
CONNOLLY, ML
通讯作者：
CONNOLLY, ML
影响因子：
8.7
作者：
Corrie BD;Marthandan N;Zimonja B;Jaglale J;Zhou Y;Barr E;Knoetze N;Breden FMW;Christley S;Scott JK;Cowell LG;Breden F
通讯作者：
Breden F
影响因子：
3.1
作者：
Christley S;Aguiar A;Blanck G;Breden F;Bukhari SAC;Busse CE;Jaglale J;Harikrishnan SL;Laserson U;Peters B;Rocha A;Schramm CA;Taylor S;Vander Heiden JA;Zimonja B;Watson CT;Corrie B;Cowell LG
通讯作者：
Cowell LG
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
DOI：
10.1056/nejmoa2102685
发表时间：
2021-10-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Dougan M;Nirula A;Azizad M;Mocherla B;Gottlieb RL;Chen P;Hebert C;Perry R;Boscia J;Heller B;Morris J;Crystal C;Igbinadolor A;Huhn G;Cardona J;Shawa I;Kumar P;Adams AC;Van Naarden J;Custer KL;Durante M;Oakley G;Schade AE;Holzer TR;Ebert PJ;Higgs RE;Kallewaard NL;Sabo J;Patel DR;Dabora MC;Klekotka P;Shen L;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators