Role of the Ebola membrane in the protection conferred by the three-mAb cocktail MIL77

MIL77, which has a higher manufacturing capacity than ZMapp, comprises MIL77-1, MIL77-2, and MIL77-3. The mechanisms by which these antibodies inhibit glycoprotein are unclear. Infection by viruses with lipid-bilayer envelopes occurs via the fusion of the viral membrane with the membrane of the target cell. Therefore, the interaction between the antibodies and the EBOV membrane is crucial. We examined the interactions between MIL77 and the viral membrane using SPR. MIL77-1 selectively binds to viral membranes, while MIL77-2 and MIL77-3 do not. MIL77-1’s ability to screen the more rigid domains of the membranes results in a locally increased concentration of the drug at the fusion site. Although MIL77-2 recognizes an epitope of GP, it is not necessary in the MIL77 cocktail. These results highlight the importance of EBOV membrane interactions in improving the efficiency of a neutralizing antibody. Furthermore, the viral membrane may be an important target of antibodies against EBOV.