Another facet of Antibody-Mediated Protection: Fc-Driven Immune Effector Function of Antibodies Against Ebola Virus Glycoprotein

Antibodies targeting the Ebola virus glycoprotein that lack neutralization activity can nonetheless offer protection by promoting activation of natural killer (NK) cells and monocyte phagocytosis.  (from Gunn et al. Cell Host Microbe

In a companion publication to the Saphire et al.Cell manuscript published online in Cell Host Microbe on August 7, 2018 Gunn et al. describe results from high throughput assays of seven different immune effector functions mediated by 168 monoclonal antibodies (mAbs) that form the VIC panel. The assays measured the ability of each of the mAbs to promote phagocytosis by human and mouse monocytes and neutrophils, as well as to activate natural killer (NK) cells isolated from human and mouse peripheral blood samples. They also used capillary electrophoresis to characterize the glycan modifications of each mAb in the panel.

In addition to the expected relationship between protection and neutralization, Gunn et al. found that mAbs that lacked significant neutralization activity were nonetheless protective. This group of mAbs tended to evoke more immune effector functions, and particular the ability to activate NK tipped the balance in favor of protection.

Immune effector functions can be engineered, so this study suggests that antibodies with Fc modifications that enhance the interface between an antibody and immune system cells can produce antibodies that have increased therapeutic efficacy.