Structure of the Inmazeb cocktail and resistance to Ebola virus escape

Cell Host Microbe. 2023 Jan 20:S1931-3128(23)00022-7. doi: 10.1016/j.chom.2023.01.002. Online ahead of print.ABSTRACTMonoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach.PMID:36708708 | DOI:10.1016/j.chom.2023.01.002

Source: Cell Host and Microbe - January 28, 2023 Category: Microbiology Authors: Vamseedhar Rayaprolu Benjamin O Fulton Ashique Rafique Emilia Arturo Dewight Williams Chitra Hariharan Heather Callaway Amar Parvate Sharon L Schendel Diptiben Parekh Sean Hui Kelly Shaffer Kristen E Pascal Elzbieta Wloga Stephanie Giordano Nicole Negron Source Type: research