A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus

被引：168

作者：

Gunn, Bronwyn M. ^{[1
]}

Yu, Wen-Han ^{[1
,2
]}

Karim, Marcus M. ^{[1
]}

Brannan, Jennifer M. ^{[3
]}

Herbert, Andrew S. ^{[3
]}

Wec, Anna Z. ^{[4
]}

Halfmann, Peter J. ^{[5
]}

Fusco, Marnie L. ^{[6
]}

Schendel, Sharon L. ^{[6
]}

Gangavarapu, Karthik ^{[6
]}

Krause, Tyler ^{[4
]}

Qiu, Xiangguo ^{[7
]}

He, Shinhua ^{[7
]}

Das, Jishnu ^{[1
,2
]}

Suscovich, Todd J. ^{[1
]}

Lai, Jonathan ^{[4
]}

Chandran, Kartik ^{[4
]}

Zeitlin, Larry ^{[8
]}

Crowe, James E., Jr. ^{[9
]}

Lauffenburger, Douglas ^{[2
]}

Kawaoka, Yoshihiro ^{[5
]}

Kobinger, Gary P. ^{[7
,10
]}

Andersen, Kristian G. ^{[11
]}

Dye, John M. ^{[3
]}

Saphire, Erica Ollmann ^{[6
]}

Alter, Galit ^{[1
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[2] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] US Army Med Res Inst Infect Dis, Virol Div, Frederick, MD 21702 USA

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

[5] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA

[6] Skaggs Inst Chem Biol, Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

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

[8] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA

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

[10] Univ Laval Quebec, Quebec City, PQ G1V 0A6, Canada

[11] Scripps Res Inst, Dept Integrat Struct & Computat Biol, Scripps Translat Sci Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

来源：

CELL HOST & MICROBE | 2018年 / 24卷 / 02期

关键词：

NEUTRALIZING ANTIBODY; IMMUNOGLOBULIN GENES; RECEPTOR ENGAGEMENT; HUMAN SURVIVOR; INFECTION; IGG; GLYCOPROTEIN; IDENTIFICATION; EPITOPES; DISEASE;

D O I：

10.1016/j.chom.2018.07.009

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens.

引用

页码：221 / +

页数：18

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