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-Structure paper
タイトル | Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection. |
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ジャーナル・号・ページ | Cell, Vol. 174, Issue 4, Page 938-952.e13, Year 2018 |
掲載日 | 2018年8月9日 |
著者 | Erica Ollmann Saphire / Sharon L Schendel / Marnie L Fusco / Karthik Gangavarapu / Bronwyn M Gunn / Anna Z Wec / Peter J Halfmann / Jennifer M Brannan / Andrew S Herbert / Xiangguo Qiu / Kshitij Wagh / Shihua He / Elena E Giorgi / James Theiler / Kathleen B J Pommert / Tyler B Krause / Hannah L Turner / Charles D Murin / Jesper Pallesen / Edgar Davidson / Rafi Ahmed / M Javad Aman / Alexander Bukreyev / Dennis R Burton / James E Crowe / Carl W Davis / George Georgiou / Florian Krammer / Christos A Kyratsous / Jonathan R Lai / Cory Nykiforuk / Michael H Pauly / Pramila Rijal / Ayato Takada / Alain R Townsend / Viktor Volchkov / Laura M Walker / Cheng-I Wang / Larry Zeitlin / Benjamin J Doranz / Andrew B Ward / Bette Korber / Gary P Kobinger / Kristian G Andersen / Yoshihiro Kawaoka / Galit Alter / Kartik Chandran / John M Dye / / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:30096313 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 16.0 - 28.0 Å |
構造データ | EMDB-7908: EMDB-7909: EMDB-7910: EMDB-7911: EMDB-7912: EMDB-7914: EMDB-7915: EMDB-7916: EMDB-7917: EMDB-7918: EMDB-7919: EMDB-7920: EMDB-7921: EMDB-7922: EMDB-7923: EMDB-7924: EMDB-7925: EMDB-7926: EMDB-7927: EMDB-7928: EMDB-7929: EMDB-7930: EMDB-7931: EMDB-7932: EMDB-7933: EMDB-7934: |
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