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A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2018 Aug 08; Vol. 24 (2), pp. 221-233.e5. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
Female
Hemorrhagic Fever, Ebola immunology
Humans
Killer Cells, Natural immunology
Mice
Mice, Inbred BALB C
Neutralization Tests
RAW 264.7 Cells
Antibodies, Monoclonal immunology
Ebolavirus immunology
Hemorrhagic Fever, Ebola prevention & control
Immunoglobulin Fc Fragments immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 30092199
- Full Text :
- https://doi.org/10.1016/j.chom.2018.07.009