Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system.

Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system in antibody-mediated protection remains unclear. In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP.