Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein.
Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein.
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DOI：
10.1016/j.immuni.2018.06.018
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发表时间：
2018-08-21
期刊：
影响因子：
32.4
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Gilchuk P;Kuzmina N;Ilinykh PA;Huang K;Gunn BM;Bryan A;Davidson E;Doranz BJ;Turner HL;Fusco ML;Bramble MS;Hoff NA;Binshtein E;Kose N;Flyak AI;Flinko R;Orlandi C;Carnahan R;Parrish EH;Sevy AM;Bombardi RG;Singh PK;Mukadi P;Muyembe-Tamfum JJ;Ohi MD;Saphire EO;Lewis GK;Alter G;Ward AB;Rimoin AW;Bukreyev A;Crowe JE Jr
埃博拉病毒在人类中引起严重的疾病，并且鉴定针对多种埃博拉病毒有效的单克隆抗体（mAb）对于治疗剂开发是重要的。在这里，我们描述了一类不同的广泛中和的人单克隆抗体，具有保护能力，对三种埃博拉病毒感染的人：埃博拉病毒（EBOV），苏丹（SUDV），和本迪布焦（BDBV）病毒。我们从埃博拉病毒病的人类幸存者中分离出mAb，并鉴定出一种有效的mAb EBOV-520，其结合糖蛋白（GP）碱基区中的表位。EBOV-520有效地中和EBOV、BDBV和SUDV，并且在这些感染的相关动物模型中也显示出保护能力。EBOV-520主要通过直接病毒中和介导保护，并表现出多功能特性。本研究鉴定了一种有效的天然mAb，并定义了可能有助于广泛保护的人抗体应答的关键特征。这种多功能mAb和相关克隆是开发广泛保护性泛埃博拉病毒治疗分子的有希望的候选者。广泛的人抗体识别埃博拉病毒GP上的四级脆弱性位点抗体具有泛埃博拉病毒中和和保护能力抗体主要通过直接病毒中和介导保护抗体使用几种机制来促进广泛的免疫性Gilchuk et al.分离并表征了对所有三种临床相关埃博拉病毒具有活性的新的广泛中和人单克隆抗体。一些有效的抗体与糖蛋白的碱基区结合，主要通过直接中和病毒起作用，并利用几种机制促进泛埃博拉病毒的保护性免疫。
Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules. Broad human antibody recognizes a quaternary site of vulnerability on ebolavirus GP The antibody possesses pan-ebolavirus neutralizing and protective capacity The antibody mediates protection principally by direct virus neutralization The antibody uses several mechanisms for contributing to broad immunity Gilchuk et al. isolated and characterized new broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolaviruses. Some potent antibodies bind to the glycoprotein base region, act principally by direct virus neutralization, and exploit several mechanisms for contributing to pan-ebolavirus protective immunity.
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影响因子：
64.5
作者：
Flyak AI;Shen X;Murin CD;Turner HL;David JA;Fusco ML;Lampley R;Kose N;Ilinykh PA;Kuzmina N;Branchizio A;King H;Brown L;Bryan C;Davidson E;Doranz BJ;Slaughter JC;Sapparapu G;Klages C;Ksiazek TG;Saphire EO;Ward AB;Bukreyev A;Crowe JE Jr
通讯作者：
Crowe JE Jr
DOI：
10.1056/nejmoa1604330
发表时间：
2016-10-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
PREVAIL II Writing Group;Multi-National PREVAIL II Study Team;Davey RT Jr;Dodd L;Proschan MA;Neaton J;Neuhaus Nordwall J;Koopmeiners JS;Beigel J;Tierney J;Lane HC;Fauci AS;Massaquoi MBF;Sahr F;Malvy D
通讯作者：
Malvy D
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
8.8
作者：
Howell KA;Brannan JM;Bryan C;McNeal A;Davidson E;Turner HL;Vu H;Shulenin S;He S;Kuehne A;Herbert AS;Qiu X;Doranz BJ;Holtsberg FW;Ward AB;Dye JM;Aman MJ
通讯作者：
Aman MJ
DOI：
10.1126/science.aaa8651
发表时间：
2015-07-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fibriansah G;Ibarra KD;Ng TS;Smith SA;Tan JL;Lim XN;Ooi JS;Kostyuchenko VA;Wang J;de Silva AM;Harris E;Crowe JE Jr;Lok SM
通讯作者：
Lok SM