从2014年埃博拉病毒疫情的一名幸存者体内分离出强效中和抗体。
Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.
作者信息
Bornholdt Zachary A, Turner Hannah L, Murin Charles D, Li Wen, Sok Devin, Souders Colby A, Piper Ashley E, Goff Arthur, Shamblin Joshua D, Wollen Suzanne E, Sprague Thomas R, Fusco Marnie L, Pommert Kathleen B J, Cavacini Lisa A, Smith Heidi L, Klempner Mark, Reimann Keith A, Krauland Eric, Gerngross Tillman U, Wittrup Karl D, Saphire Erica Ollmann, Burton Dennis R, Glass Pamela J, Ward Andrew B, Walker Laura M
机构信息
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Science. 2016 Mar 4;351(6277):1078-83. doi: 10.1126/science.aad5788. Epub 2016 Feb 18.
Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.
靶向埃博拉病毒表面糖蛋白（EBOV GP）的抗体与抵御致死性疾病有关，但人类针对EBOV GP的抗体反应特征仍知之甚少。我们从一名在2014年埃博拉病毒扎伊尔疫情中幸存的康复期供体的外周B细胞中分离并鉴定了349种GP特异性单克隆抗体（mAb）。值得注意的是，77%的mAb能中和活的埃博拉病毒，并且有几种mAb表现出前所未有的效力。与GP结合的选定mAb的结构揭示了一个位于病毒膜近端的GP茎区的脆弱位点。靶向该位点的中和抗体在小鼠中对致死性埃博拉病毒攻击显示出强大的治疗效果。这些结果为设计新的埃博拉病毒候选疫苗和免疫疗法提供了框架。
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