A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.
A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.
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FC工程方法定义了针对埃博拉病毒的免疫力的功能体液相关性。
DOI：
10.1016/j.immuni.2021.03.009
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发表时间：
2021-04-13
期刊：
影响因子：
32.4
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Gunn BM;Lu R;Slein MD;Ilinykh PA;Huang K;Atyeo C;Schendel SL;Kim J;Cain C;Roy V;Suscovich TJ;Takada A;Halfmann PJ;Kawaoka Y;Pauthner MG;Momoh M;Goba A;Kanneh L;Andersen KG;Schieffelin JS;Grant D;Garry RF;Saphire EO;Bukreyev A;Alter G
保护性埃博拉病毒（EBOV）抗体具有中和活性和诱导fc介导的先天免疫效应功能。增强fc效应物功能的努力通常集中在最大化抗体依赖的细胞毒性上，然而不同的功能组合可能对抗体介导的保护至关重要。由于已经从EBOV疾病幸存者中克隆了中和抗体，我们试图确定幸存者fc效应谱，以帮助指导fc优化策略。幸存者产生了一系列功能性抗体反应，因此我们应用了快速、高通量的fc工程平台来定义最具保护性的基因图谱。我们从EBOV中和抗体中生成了具有相同fab的fc变异体库。在严格的小鼠体内模型中，具有抗体介导的补体沉积和适度NK细胞活性的fc变异体显示出完全的保护活性。我们的研究结果强调了特异性效应功能在抗体介导的保护中的重要性，实验平台为识别免疫相关因子以指导治疗性抗体设计提供了可推广的资源。Gunn等人分析了埃博拉病毒病幸存者，并应用了一个工程抗体Fc结构域的平台来定义保护性谱。具有补体沉积的fc变异体，但适度的NK细胞活性完全保护感染小鼠免受疾病。该实验平台可用于鉴定对其他病原体的免疫相关因素，并指导治疗性抗体的设计。
Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of Fc-mediated innate immune effector functions. Efforts to enhance Fc-effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions may be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc-effector profiles to help guide Fc-optimization strategies. Survivors developed a range of functional antibody responses, and we therefore applied a rapid, high-throughput Fc-engineering platform to define the most protective profiles. We generated a library of Fc-variants with identical Fabs from an EBOV neutralizing antibody. Fc-variants with antibody-mediated complement deposition and moderate NK cell activity demonstrated complete protective activity in a stringent in vivo mouse model. Our findings highlight the importance of specific effector functions in antibody-mediated protection and the experimental platform presents a generalizable resource for identifying correlates of immunity to guide therapeutic antibody design. Gunn et al. profile Ebola virus disease survivors and apply a platform for engineering antibody Fc domains to define protective profiles. Fc-variants with complement deposition, yet moderate NK cell activity completely protected infected mice from disease. This experimental platform can be used for identifying correlates of immunity to other pathogens, and to guide therapeutic antibody design.
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影响因子：
32.4
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
通讯作者：
Crowe JE Jr
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
免疫途径定义了疫苗介导的对SIV的保护的多种机制。
影响因子：
82.9
作者：
Ackerman ME;Das J;Pittala S;Broge T;Linde C;Suscovich TJ;Brown EP;Bradley T;Natarajan H;Lin S;Sassic JK;O'Keefe S;Mehta N;Goodman D;Sips M;Weiner JA;Tomaras GD;Haynes BF;Lauffenburger DA;Bailey-Kellogg C;Roederer M;Alter G
通讯作者：
Alter G
影响因子：
3.7
作者：
Engler, Carola;Kandzia, Romy;Marillonnet, Sylvestre
通讯作者：
Marillonnet, Sylvestre
DOI：
10.1073/pnas.1609316113
发表时间：
2016-10-18
影响因子：
11.1
作者：
He, Wenqian;Tan, Gene S.;Miller, Matthew S.
通讯作者：
Miller, Matthew S.