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

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

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

2018

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. : In this paper, Kuzmina et al. demonstrate that filovirus antibodies from human survivors present at low concentrations are capable of enhancement of infection, suggesting that low levels of antibodies in humans may facilitate virus spread. The enhancement can be caused by antibodies of various epitope specificities, neutralizing capacities, and subclasses. Keywords: Ebola virus, filovirus, antibody, enhancement of infection, FC receptor, epitope

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