Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP_(1,2) in a position elevated from the virion membrane.

ABSTRACT: Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP_1,2) are the standard of care for Ebola virus disease (EVD). Anti-GP_1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP_1,2 epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk-MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP_1,2 that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6

SUBMITTER: Hastie KM 

PROVIDER: S-EPMC11791206 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature