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
Affiliations
Natalia A. Kuzmina
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Patrick Younan
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Pavlo Gilchuk
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Rodrigo I. Santos
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Andrew I. Flyak
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA
Philipp A. Ilinykh
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Kai Huang
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Ndongala M. Lubaki
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
Palaniappan Ramanathan
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA
James E. Crowe, Jr.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Corresponding author
Alexander Bukreyev
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Corresponding author
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
