A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
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DOI：
10.1016/j.chom.2018.07.009
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发表时间：
2018-08-08
影响因子：
30.3
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Gunn BM;Yu WH;Karim MM;Brannan JM;Herbert AS;Wec AZ;Halfmann PJ;Fusco ML;Schendel SL;Gangavarapu K;Krause T;Qiu X;He S;Das J;Suscovich TJ;Lai J;Chandran K;Zeitlin L;Crowe JE Jr;Lauffenburger D;Kawaoka Y;Kobinger GP;Andersen KG;Dye JM;Saphire EO;Alter G
最近的埃博拉病毒（EBOV）流行突出了对有效疫苗和治疗方法的需求，以限制/预防疫情。针对EBOV的宿主抗体对于控制疾病是至关重要的，并且重组单克隆抗体（mAb）可以保护免受感染。然而，抗体介导一系列抗病毒功能，包括中和以及免疫细胞上Fc结构域受体的接合，导致吞噬作用或NK细胞介导的对感染细胞的杀伤。因此，为了理解介导EBOV保护的抗体特征，我们使用EBOV特异性mAb文库检查了与保护相关的特异性Fc特征。中和与针对EBOV的治疗保护强烈相关。然而，几种中和性mAb未能保护，而几种非中和性或弱中和性mAb可以保护。抗体介导的效应子功能，包括吞噬作用和NK细胞活化与保护作用相关，特别是对于具有中等中和活性的抗体。该框架确定了可以为针对EBOV和其他病原体的治疗和疫苗设计策略提供信息的功能相关性。虽然抗体可以提供针对埃博拉病毒的保护，但其机制尚不清楚。古恩等人使用埃博拉病毒特异性抗体文库剖析了Fc功能对保护的贡献。Fc功能是中和抗体和非中和抗体之间保护作用的关键预测因子，表明Fc和Fab介导的抗体功能对埃博拉病毒的协同作用。
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit/prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc-features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens. While antibodies provide protection against Ebola virus, the mechanism is unclear. Gunn et al. dissect the contribution of Fc-functions to protection using a library of Ebola virus-specific antibodies. Fc-function was a critical predictor of protection across neutralizing and non-neutralizing antibodies, pointing to synergy between Fc- and Fab-mediated antibody-functions against Ebola.
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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
影响因子：
5.4
作者：
Ackerman, Margaret E.;Dugast, Anne-Sophie;Alter, Galit
通讯作者：
Alter, Galit
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：
4.4
作者：
Herter, Sylvia;Birk, Martina C.;Bacac, Marina
通讯作者：
Bacac, Marina
影响因子：
64.5
作者：
DiLillo DJ;Ravetch JV
通讯作者：
Ravetch JV