@article{296223a9b3d749d88b2f1d3abedbf463,
title = "Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection",
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. The systematic assessment of the effector functions and binding sites of antibodies against Ebola virus provides a generalizable framework to evaluate the determinants of antibody-mediated protection in viral disease.",
keywords = "antibody, consortium, ebola virus, epitope, glycoprotein, neutralization, protection",
author = "{the Viral Hemorrhagic Fever Immunotherapeutic Consortium} and Saphire, {Erica Ollmann} and Schendel, {Sharon L.} and Fusco, {Marnie L.} and Karthik Gangavarapu and Gunn, {Bronwyn M.} and Wec, {Anna Z.} and Halfmann, {Peter J.} and Brannan, {Jennifer M.} and Herbert, {Andrew S.} and Xiangguo Qiu and Kshitij Wagh and Shihua He and Giorgi, {Elena E.} and James Theiler and Pommert, {Kathleen B.J.} and Krause, {Tyler B.} and Turner, {Hannah L.} and Murin, {Charles D.} and Jesper Pallesen and Edgar Davidson and Rafi Ahmed and Aman, {M. Javad} and Alexander Bukreyev and Burton, {Dennis R.} and Crowe, {James E.} and Davis, {Carl W.} and George Georgiou and Florian Krammer and Kyratsous, {Christos A.} and Lai, {Jonathan R.} and Cory Nykiforuk and Pauly, {Michael H.} and Pramila Rijal and Ayato Takada and Townsend, {Alain R.} and Viktor Volchkov and Walker, {Laura M.} and Wang, {Cheng I.} and Larry Zeitlin and Doranz, {Benjamin J.} and Ward, {Andrew B.} and Bette Korber and Kobinger, {Gary P.} and Andersen, {Kristian G.} and Yoshihiro Kawaoka and Galit Alter and Kartik Chandran and Dye, {John M.}",
note = "Funding Information: The major support for this project was U19 AI109762, a Centers of Excellence in Translational Research Award of NIAID. We thank the over 200 individuals who contributed their time, reagents and expertise. We also thank Julius Lutwama (UVRI), Leslie Lobel (Ben Gurion), Robert Garry and James Robinson (Tulane), Frederick Holtsberg (IBT), Luis Branco (Zalgen), Armand Sprecher (MSF), Lisa Hensley (NIAID IRF), and Heinz Feldmann (NIAID RML) for valuable discussions. This is manuscript #29635 of TSRI. Alanine scanning was done under NIAID contract HHSN272201400058C to B.J.D.; C.I.W. was supported by Human Therapeutic Monoclonal Antibodies Platform IAF311007; K.G.A. acknowledges additional support from NIAID U19AI135995. Funding Information: The major support for this project was U19 AI109762 , a Centers of Excellence in Translational Research Award of NIAID . We thank the over 200 individuals who contributed their time, reagents and expertise. We also thank Julius Lutwama (UVRI), Leslie Lobel (Ben Gurion), Robert Garry and James Robinson (Tulane), Frederick Holtsberg (IBT), Luis Branco (Zalgen), Armand Sprecher (MSF), Lisa Hensley (NIAID IRF), and Heinz Feldmann (NIAID RML) for valuable discussions. This is manuscript #29635 of TSRI. Alanine scanning was done under NIAID contract HHSN272201400058C to B.J.D.; C.I.W. was supported by Human Therapeutic Monoclonal Antibodies Platform IAF311007 ; K.G.A. acknowledges additional support from NIAID U19AI135995 . Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = aug,
day = "9",
doi = "10.1016/j.cell.2018.07.033",
language = "English (US)",
volume = "174",
pages = "938--952.e13",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}
