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

被引：149

作者：

Saphire, Erica Ollmann ^{[1
]}

Schendel, Sharon L. ^{[1
]}

Fusco, Marnie L. ^{[1
]}

Gangavarapu, Karthik ^{[1
]}

Gunn, Bronwyn M. ^{[3
]}

Wec, Anna Z. ^{[4
]}

Halfmann, Peter J. ^{[6
]}

Brannan, Jennifer M. ^{[7
]}

Herbert, Andrew S. ^{[7
]}

Qiu, Xiangguo ^{[8
]}

Wagh, Kshitij ^{[9
]}

He, Shihua ^{[9
]}

Giorgi, Elena E. ^{[9
]}

Theiler, James ^{[9
]}

Pommert, Kathleen B. J. ^{[1
]}

Krause, Tyler B. ^{[4
]}

Turner, Hannah L. ^{[2
]}

Murin, Charles D. ^{[2
]}

Pallesen, Jesper ^{[2
]}

Davidson, Edgar ^{[10
]}

Ahmed, Rafi ^{[11
]}

Aman, M. Javad ^{[12
]}

Bukreyev, Alexander ^{[13
]}

Burton, Dennis R. ^{[1
]}

Crowe, James E., Jr. ^{[14
]}

Davis, Carl W. ^{[11
]}

Georgiou, George ^{[15
]}

Krammer, Florian ^{[16
]}

Kyratsous, Christos A. ^{[17
]}

Lai, Jonathan R. ^{[5
]}

Nykiforuk, Cory ^{[18
]}

Pauly, Michael H. ^{[19
]}

Rijal, Pramila ^{[20
]}

Takada, Ayato ^{[21
]}

Townsend, Alain R. ^{[20
]}

Volchkov, Viktor ^{[22
]}

Walker, Laura M. ^{[23
]}

Wang, Cheng-I. ^{[24
]}

Zeitlin, Larry ^{[19
]}

Doranz, Benjamin J. ^{[10
]}

Ward, Andrew B. ^{[2
]}

Korber, Bette ^{[9
]}

Kobinger, Gary P. ^{[25
]}

Andersen, Kristian G. ^{[1
]}

Kawaoka, Yoshihiro ^{[6
]}

Alter, Galit ^{[3
]}

Chandran, Kartik ^{[4
]}

Dye, John M. ^{[7
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Ragon Inst, Cambridge, MA 02139 USA

[4] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[5] Albert Einstein Coll Med, Biochem, Bronx, NY 10461 USA

[6] Univ Wisconsin, Div Pathobiol Sci, Madison, WI 53706 USA

[7] US Army Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA

[8] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg R3E 3R2, MB, Canada

[9] Los Alamos Natl Lab, Los Alamos, NM 87545 USA

[10] Integral Mol, Philadelphia, PA 19104 USA

[11] Emory Univ, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA

[12] Integrated BioTherapeut, Rockville, MD 20850 USA

[13] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA

[14] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA

[15] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA

[16] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[17] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

[18] Emergent BioSolut, Winnipeg, MB R3T 5Y3, Canada

[19] Mapp Biopharmaceut, San Diego, CA 92121 USA

[20] Univ Oxford, Human Immunol Unit, Oxford OX3 9DS, England

[21] Hokkaido Univ, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0010020, Japan

[22] Univ Lyon, INSERM CNRS, Lyon, France

[23] Adimab LLC, Lebanon, NH 03766 USA

[24] ASTAR, Singapore 138648, Singapore

[25] Univ Laval, Dept Microbiol Infectiol & Immunol, Med, Quebec City, PQ G1V O46, Canada

来源：

CELL | 2018年 / 174卷 / 04期

关键词：

NATURAL-KILLER-CELLS; NONNEUTRALIZING ANTIBODIES; MEDIATED NEUTRALIZATION; VIRION GLYCOPROTEINS; INFECTION; EPITOPES; MOUSE; IDENTIFICATION; BINDING; ENTRY;

D O I：

10.1016/j.cell.2018.07.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. Unex-pectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.

引用

页码：938 / +

页数：28

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