Cell Reports
Volume 24, Issue 10, 4 September 2018, Pages 2723-2732.e4
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Article
Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop

https://doi.org/10.1016/j.celrep.2018.08.009Get rights and content
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Highlights

  • Structures of BDBV GP and EBOV Makona GP reveal similarities to other filoviral GPs

  • Pan-ebolavirus antibody ADI-15878 targets conserved residues on HR1 and the IFL

  • Comparing apo- and bound-ADI-15878 suggests an induced-fit mechanism for binding to GP

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 antibody 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 the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery.

Keywords

Ebola virus
Bundibugyo virus
pan-filoviral
filovirus
antibody
glycoprotein

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