Structural and molecular basis for Ebola virus neutralization by protective human antibodies

被引：162

作者：

Misasi, John ^{[1
,5
,8
]}

Gilman, Morgan S. A. ^{[2
]}

Kanekiyo, Masaru ^{[1
]}

Gui, Miao ^{[4
]}

Cagigi, Alberto ^{[1
]}

Mulangu, Sabue ^{[1
]}

Corti, Davide ^{[6
]}

Ledgerwood, Julie E. ^{[1
]}

Lanzavecchia, Antonio ^{[6
,9
]}

Cunningham, James ^{[5
]}

Muyembe-Tamfun, Jean Jacques ^{[7
]}

Baxa, Ulrich ^{[3
]}

Graham, Barney S. ^{[1
]}

Xiang, Ye ^{[4
]}

Sullivan, Nancy J. ^{[1
]}

McLellan, Jason S. ^{[2
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[2] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA

[3] Leidos Biomed Res Inc, Electron Microscopy Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[4] Tsinghua Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing Adv Innovat Ctr Struct Biol, Ctr Infect Dis Res,Dept Basic Med Sci,Sch Med, Beijing 100084, Peoples R China

[5] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA

[6] Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[7] Natl Lab Publ Hlth, Natl Inst Biomed Res, BP 1197, Kinshasa, DEM REP CONGO

[8] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02215 USA

[9] Swiss Fed Inst Technol, Inst Microbiol, CH-8093 Zurich, Switzerland

来源：

SCIENCE | 2016年 / 351卷 / 6279期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

MEDIATED NEUTRALIZATION; CONFORMATIONAL EPITOPE; ENTRY REQUIRES; GLYCOPROTEIN; RESIDUES; INFECTION; COMPLEX;

D O I：

10.1126/science.aad6117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

引用

页码：1343 / 1346

页数：4

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