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The Zaire ebolavirus glycoprotein (GP) is the primary surface protein of the Ebola virus, essential for viral attachment to host cells and subsequent membrane fusion (UniProt P87666). It is expressed as a trimeric complex of GP1 and GP2 subunits, where GP1 handles receptor binding and GP2 facilitates fusion (Rayaprolu et al., 2022). Additionally, infected cells secrete a dimeric form known as soluble GP (sGP), which shares the N-terminal domain of GP1 and serves as an immune decoy to divert the host's antibody response (Rayaprolu et al., 2022). Odesivimab (REGN3471) is a human monoclonal antibody that specifically targets an epitope on the GP1 head and sGP (Drugs.com; Rayaprolu et al., 2022). While odesivimab is largely non-neutralizing, it provides therapeutic efficacy by binding to the decoy sGP and inducing Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), to eliminate infected cells (FDA Label; Regeneron). As a component of the Inmazeb cocktail, it represents a critical advancement in the treatment of Ebola virus disease, the first such therapy to receive FDA approval (Regeneron).
Odesivimab binds to the GP1 head of the surface glycoprotein (GP1,2) and the soluble glycoprotein (sGP), inducing antibody-dependent effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via Fc gamma receptor signaling (Rayaprolu et al., 2022; FDA Label).
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