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.

Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines

“…Distinct patterns of antibody response were observed, suggesting the elicitation of NAbs and c13C6-like non-NAbs. Among the three trimer groups, while GPECTO showed a moderate NAb response with signs of enhancement observed for 2-4 mice, an increase in both NAb and c13C6-like responses was noted for GP∆muc, suggesting that the removal of MLD exposes both NAb epitopes and the glycan cap, which is a main target for ADE-causing antibodies in human infection (25). The WL 2 P 2 mutation appeared to have largely reversed the adverse effect caused by the MLD removal.…”

Letter to the Editor: Issues on COVID-19 Pathogenesis

“…Antibody-dependent enhancement (ADE) resulting from successive infections by antigenically related viruses has been extensively described and recognized as an important mechanism of viral pathogenesis. In vitro and/or in vivo evidence of ADE has been reported for several viruses, such as human immunodeficiency (11), influenza (28), Ebola (18) and dengue (DENV) viruses (10).…”

Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein

“…In this context, antibodymediated uptake of virus may increase viral replication and potentially enhance disease. The phenomenon of antibody-dependent enhancement (ADE) of disease was shown in vitro with Zika and dengue viruses and also for a number of other virus families, including the Filoviridae and Togaviridae (34,35).…”