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

Abstract

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.

Figure 1

Panels (a,c). Representative sensograms of the binding between various concentrations of MIL77-1 and the lipid bilayer (L1 chip), POPC (panel a), DPPC(panel b), POPC/Chol(2:1w/w) (panel c). (Panels d–f) The corresponding relationships between the equilibrium binding response (RUeq) and the MIL77-1 concentration (C) (circles). The data were fit using the BIAcore’s steady-state affinity model(lines). MIL77-1 concentrations used are 1.25, 2.5, 5, 10, 20 and 40 μM.

Figure 2

The two-state fitting model of the binding sensograms between various concentrations of MIL77-1 and the lipid bilayer (L1 chip), POPC (panel a), POPC/DPPC(1:1w/w) (panel b), DPPC(panel c), POPC/Chol(2:1w/w) (panel d), POPG (panel e). MIL77-1 concentrations used are 1.25, 2.5, 5, 10, 20 and 40 μM. Black curve is fitting result. Color curve is binding result.