Cell Reports
Volume 24, Issue 7, 14 August 2018, Pages 1802-1815.e5
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Article
Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors

https://doi.org/10.1016/j.celrep.2018.07.035Get rights and content
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Highlights

  • mAbs from filovirus human survivors tested for their ability to facilitate ADE

  • ADE is not restricted to a particular epitope, neutralizing capacity, or subclass

  • Lower-affinity interactions still cause ADE

  • ADE counteracts antibody-mediated protection and facilitates infection

Summary

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.

Keywords

Ebola virus
filovirus
antibody
enhancement of infection
FC receptor
epitope

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Present address: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA

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