Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

被引：148

作者：

Flyak, Andrew I. ^{[1
]}

Shen, Xiaoli ^{[5
]}

Murin, Charles D. ^{[8
,9
]}

Turner, Hannah L. ^{[8
]}

David, Joshua A. ^{[8
]}

Fusco, Marnie L. ^{[9
]}

Lampley, Rebecca ^{[3
]}

Kose, Nurgun ^{[3
]}

Ilinykh, Philipp A. ^{[5
]}

Kuzmina, Natalia ^{[5
]}

Branchizio, Andre ^{[3
]}

King, Hannah ^{[3
]}

Brown, Leland ^{[3
]}

Bryan, Christopher ^{[11
]}

Davidson, Edgar ^{[11
]}

Doranz, Benjamin J. ^{[11
]}

Slaughter, James C. ^{[3
,4
]}

Sapparapu, Gopal ^{[3
]}

Klages, Curtis ^{[7
]}

Ksiazek, Thomas G. ^{[5
,6
,7
]}

Saphire, Erica Ollmann ^{[9
,10
]}

Ward, Andrew B. ^{[8
]}

Bukreyev, Alexander ^{[5
,6
,7
]}

Crowe, James E., Jr. ^{[1
,2
,3
]}

机构：

[1] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA

[5] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA

[6] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

[7] Galveston Natl Lab, Galveston, TX 77550 USA

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

[9] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[10] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[11] Integral Mol Inc, Philadelphia, PA 19104 USA

来源：

CELL | 2016年 / 164卷 / 03期

基金：

美国国家科学基金会;

关键词：

NIEMANN-PICK C1; MONOCLONAL-ANTIBODIES; VIRUS GLYCOPROTEIN; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; ZAIRE-EBOLAVIRUS; STRUCTURAL BASIS; MARBURG VIRUS; SYSTEM;

D O I：

10.1016/j.cell.2015.12.022

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：

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

引用

页码：392 / 405

页数：14

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