2018
DOI: 10.1016/j.celrep.2018.08.009
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Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop

Abstract: SUMMARY Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The anti body ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/ Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe t… Show more

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Cited by 30 publications
(31 citation statements)
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“…In contrast, ADI-15946, an antibody that competes with KZ52 but bridges the GP1 core and glycan cap [33][34][35], modestly stabilized the high-FRET state. We also tested nAbs ADI-15878 and ADI-15742, which contact the GP2 fusion loop and adjacent GP1 protomer [33,34,36]. These nAbs significantly increased the occupancy in the high-FRET state (Figure 5b).…”
Section: Neutralizing Antibodies Mediate Gp Conformationmentioning
confidence: 99%
“…In contrast, ADI-15946, an antibody that competes with KZ52 but bridges the GP1 core and glycan cap [33][34][35], modestly stabilized the high-FRET state. We also tested nAbs ADI-15878 and ADI-15742, which contact the GP2 fusion loop and adjacent GP1 protomer [33,34,36]. These nAbs significantly increased the occupancy in the high-FRET state (Figure 5b).…”
Section: Neutralizing Antibodies Mediate Gp Conformationmentioning
confidence: 99%
“…Engineered glycoprotein trimers from other enveloped viruses (e.g., Middle East respiratory syndrome coronavirus, MERS-CoV, and parainfluenza virus types 1-4) were designed to present the antigenically optimal prefusion conformation Stewart-Jones et al 2018). Glycoproteins from Ebola virus were modified by removing the mucin-like domain, assembled as soluble trimers, and then studied in a complex with the ADI-15878 Fab by SPA (Murin et al 2018). Except for the above-mentioned trimeric forms, glycoprotein complexes containing more than one viral glycoprotein (e.g., gH/gL/gp42 from Epstein-Barr virus) have also been used for cryo-EM antibody-antigen studies (Snijder et al 2018).…”
Section: Enveloped Viruses Without Icosahedral Symmetrymentioning
confidence: 99%
“…Because GP→GP CL cleavage is a prerequisite for cell entry by all filoviruses that have been evaluated to date (22,24,47), we postulated that this cleavage also destabilizes GPs from divergent ebolaviruses. Accordingly, we used the pan-ebolavirus base-binding mAb ADI-15878 to probe the thermal stability of GPs from the divergent ebolaviruses Sudan virus (SUDV) and the recently discovered Bombali virus (BOMV) in the epitope-loss ELISA (48)(49)(50)(51). THL cleavage of SUDV GP and BOMV GP was verified by western blot ( Fig 3A).…”
Section: The Gp Proteins Of Other Ebolaviruses Are Also Destabilized mentioning
confidence: 99%