Literature DB >> 30096313

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.

Erica Ollmann Saphire1, Sharon L Schendel2, Marnie L Fusco2, Karthik Gangavarapu2, Bronwyn M Gunn3, Anna Z Wec4, Peter J Halfmann5, Jennifer M Brannan6, Andrew S Herbert6, Xiangguo Qiu7, Kshitij Wagh8, Shihua He7, Elena E Giorgi8, James Theiler8, Kathleen B J Pommert2, Tyler B Krause4, Hannah L Turner9, Charles D Murin9, Jesper Pallesen9, Edgar Davidson10, Rafi Ahmed11, M Javad Aman12, Alexander Bukreyev13, Dennis R Burton2, James E Crowe14, Carl W Davis11, George Georgiou15, Florian Krammer16, Christos A Kyratsous17, Jonathan R Lai18, Cory Nykiforuk19, Michael H Pauly20, Pramila Rijal21, Ayato Takada22, Alain R Townsend21, Viktor Volchkov23, Laura M Walker24, Cheng-I Wang25, Larry Zeitlin20, Benjamin J Doranz10, Andrew B Ward9, Bette Korber8, Gary P Kobinger26, Kristian G Andersen27, Yoshihiro Kawaoka28, Galit Alter29, Kartik Chandran30, John M Dye31.   

Abstract

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.
Copyright © 2018 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  antibody; consortium; ebola virus; epitope; glycoprotein; neutralization; protection

Mesh：

Substances：

Year:  2018        PMID： 30096313      PMCID： PMC6102396          DOI： 10.1016/j.cell.2018.07.033

Source DB:  PubMed          Journal:  Cell        ISSN： 0092-8674            Impact factor:   41.582


  82 in total

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