A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus
Name
nihms-991959.pdf
Description
Accepted version
Size
2.78 MB
Format
Adobe PDF
Checksum (MD5)
95a45f4a35adb8441cd26e1ccf3b4fab
Author(s)
Yu, Wen-Han
Das, Jishnu
Lauffenburger, Douglas A
Alter, Galit
Date Issued
August 2018
Journal
Cell host & microbe
Publisher
Elsevier BV
Citation
Gunn, Bronwyn M. et al. “A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.” Cell host & microbe, vol. 24, no. 2, 2018, pp. 221-233.e5 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
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. While antibodies provide protection against Ebola virus, the mechanism is unclear. Gunn et al. dissect the contribution of Fc-functions to protection using a library of Ebola virus-specific antibodies. Fc function was a critical predictor of protection across neutralizing and non-neutralizing antibodies, pointing to synergy between Fc- and Fab-mediated antibody-functions against Ebola.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CHOM.2018.07.009
