Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors.

Abstract

Some monoclonal antibodies (mAbs) recovered from survivors of filovirus infections can protect against infection. It is currently unknown whether natural infection also induces some antibodies with the capacity for antibody-dependent enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub-neutralizing concentrations, and this effect was not restricted to mAbs with a particular epitope specificity, neutralizing capacity, or subclass. Blocking of specific Fcγ receptors reduced but did not abolish ADE that was associated with high-affinity binding antibodies, suggesting that lower-affinity interactions still cause ADE. Mutations of Fc fragments of an mAb that altered its interaction with Fc receptors rendered the antibody partially protective in vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection and facilitates dissemination of filovirus infections.

• Authors: Natalia A Kuzmina, Patrick Younan, Pavlo Gilchuk, Rodrigo I Santos, Andrew I Flyak, Philipp A Ilinykh, Kai Huang, Ndongala M Lubaki, Palaniappan Ramanathan, James E Crowe Jr, Alexander Bukreyev
• Journal: Cell reports (Cell Rep) Vol. 24 Issue 7 Pg. 1802-1815.e5 (08 14 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 30110637 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• Epitopes
• Immune Sera
• Immunoglobulin Fc Fragments
• Receptors, IgG
• Viral Envelope Proteins
• enhanced green fluorescent protein
• Green Fluorescent Proteins

Topics

• Animals
• Antibodies, Monoclonal (isolation & purification, pharmacology)
• Antibodies, Neutralizing (isolation & purification, pharmacology)
• Antibodies, Viral (isolation & purification, pharmacology)
• Antibody-Dependent Enhancement
• Ebolavirus (drug effects, genetics, immunology, pathogenicity)
• Epitopes (genetics, immunology)
• Gene Expression
• Genes, Reporter
• Green Fluorescent Proteins (genetics, metabolism)
• Hemorrhagic Fever, Ebola (immunology, mortality, therapy, virology)
• Humans
• Immune Sera (chemistry)
• Immunoglobulin Fc Fragments (chemistry, genetics)
• Marburg Virus Disease (immunology, mortality, therapy, virology)
• Marburgvirus (drug effects, genetics, pathogenicity)
• Mice
• Mice, Inbred BALB C
• Monocytes (drug effects, immunology, virology)
• Primary Cell Culture
• Receptors, IgG (genetics, immunology)
• Survival Analysis
• Survivors
• THP-1 Cells
• Viral Envelope Proteins (genetics, immunology)