Format

Send to

Choose Destination
Cell Host Microbe. 2018 Aug 8;24(2):221-233.e5. doi: 10.1016/j.chom.2018.07.009.

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

Author information

1
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
2
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
4
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin, Madison, WI 53706, USA.
6
Department of Immunology and Microbiology, The Scripps Research Institute, The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
7
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
8
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA.
9
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
10
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
11
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Université Laval Quebec, Québec, QC G1V 0A6, Canada.
12
Department of Immunology and Microbial Science, Scripps Translational Science Institute, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
13
Department of Immunology and Microbiology, The Scripps Research Institute, The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA. Electronic address: erica@scripps.edu.
14
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@partners.org.

Abstract

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.

KEYWORDS:

Ebola virus; Fc-receptors; antibodies; effector function; immunotherapeutics; innate immunity; phagocytosis

PMID:
30092199
DOI:
10.1016/j.chom.2018.07.009

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center