Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
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DOI：
10.1016/j.cell.2018.07.033
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发表时间：
2018-08-09
期刊：
影响因子：
64.5
通讯作者：
Viral Hemorrhagic Fever Immunotherapeutic Consortium
中科院分区：
文献类型：
--
作者：
Saphire EO;Schendel SL;Fusco ML;Gangavarapu K;Gunn BM;Wec AZ;Halfmann PJ;Brannan JM;Herbert AS;Qiu X;Wagh K;He S;Giorgi EE;Theiler J;Pommert KBJ;Krause TB;Turner HL;Murin CD;Pallesen J;Davidson E;Ahmed R;Aman MJ;Bukreyev A;Burton DR;Crowe JE Jr;Davis CW;Georgiou G;Krammer F;Kyratsous CA;Lai JR;Nykiforuk C;Pauly MH;Rijal P;Takada A;Townsend AR;Volchkov V;Walker LM;Wang CI;Zeitlin L;Doranz BJ;Ward AB;Korber B;Kobinger GP;Andersen KG;Kawaoka Y;Alter G;Chandran K;Dye JM;Viral Hemorrhagic Fever Immunotherapeutic Consortium
抗体有望在暴露后治疗新出现的病毒，但哪些抗体特征和体外检测最具预测性尚不清楚。我们的国际联盟使用多学科分析系统地评估了针对埃博拉病毒(EBOV)的抗体。对于每种抗体，我们评估了病毒表面糖蛋白(GP)和分泌型糖蛋白(SGP)上识别的表位、多次中和试验的读数、未中和的病毒粒子的比例、多糖结构、诱导的吞噬细胞和自然杀伤细胞功能，以及在小鼠挑战模型中的体内保护。多重免疫效应功能(IEF)的中和和诱导与保护最为密切相关。中和主要是通过维持在内体裂解的GP上的表位发生的，而最大的IEF映射到距离病毒膜最远的表位。出乎意料的是，SGP的交叉反应并没有显著影响体内保护。这一全面的数据集为评估新的抗体和疫苗反应提供了一个标准，并为EBOV和相关病毒的治疗开发提供了路线图。对抗埃博拉病毒抗体的效应器功能和结合部位的系统评估为评估病毒疾病中抗体中介保护的决定因素提供了一个普遍的框架。
Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses. The systematic assessment of the effector functions and binding sites of antibodies against Ebola virus provides a generalizable framework to evaluate the determinants of antibody-mediate protection in viral disease.
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影响因子：
6.7
作者：
Fusco ML;Hashiguchi T;Cassan R;Biggins JE;Murin CD;Warfield KL;Li S;Holtsberg FW;Shulenin S;Vu H;Olinger GG;Kim DH;Whaley KJ;Zeitlin L;Ward AB;Nykiforuk C;Aman MJ;Berry JD;Saphire EO
通讯作者：
Saphire EO
影响因子：
--
作者：
Hasegawa H;van Reit E;Kida H
通讯作者：
Kida H
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影响因子：
4.6
作者：
Audet J;Wong G;Wang H;Lu G;Gao GF;Kobinger G;Qiu X
通讯作者：
Qiu X
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
影响因子：
5.4
作者：
Dube, Derek;Brecher, Matthew B.;White, Judith M.
通讯作者：
White, Judith M.