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A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus

2018; Cell Press; Volume: 24; Issue: 2 Linguagem: Inglês

10.1016/j.chom.2018.07.009

1934-6069

Bronwyn M. Gunn, Wen‐Han Yu, Marcus M. Karim, Jennifer M. Brannan, Andrew S. Herbert, Anna Z. Wec, Peter Halfmann, Marnie L. Fusco, Sharon L. Schendel, Karthik Gangavarapu, Tyler B. Krause, Xiangguo Qiu, Shinhua He, Jishnu Das, Todd J. Suscovich, Jonathan R. Lai, Kartik Chandran, Larry Zeitlin, James E. Crowe, Douglas A. Lauffenburger, Yoshihiro Kawaoka, Gary Kobinger, Kristian G. Andersen, John M. Dye, Erica Ollmann Saphire, Galit Alter,

Virus-based gene therapy research

The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens.