A broadly-neutralizing antibody against Ebolavirus glycoprotein that potentiates the breadth and neutralization potency of other antibodies

Francesca R. Donnellan; Vamseedhar Rayaprolu; Pramila Rijal; Victoria O’Dowd; Amar D. Parvate; Heather Callaway; Chitra Hariharan; Dipti Parekh; Sean Hui; Kelly C. L. Shaffer; Rubén Díaz-Avalos; Kathryn M. Hastie; Lisa M. Schimanski; Helena Müller-Kräuter; Thomas Strecker; Ariane Balaram; Peter Halfmann; Erica Ollmann Saphire; Daniel J. Lightwood; Alain R. Townsend; Simon J. Draper

doi:10.1038/s44298-026-00192-7

Immunologynpj VirusesMay 7, 2026

Peer-reviewed journal article

A broadly-neutralizing antibody against Ebolavirus glycoprotein that potentiates the breadth and neutralization potency of other antibodies

Francesca R. Donnellan iD, Vamseedhar Rayaprolu iD, Pramila Rijal iD, Victoria O’Dowd, Amar D. Parvate iD, Heather Callaway iD, Chitra Hariharan iD, Dipti Parekh, Sean Hui iD, Kelly C. L. Shaffer iD, Rubén Díaz-Avalos iD, Kathryn M. Hastie iD, Lisa M. Schimanski, Helena Müller-Kräuter iD, Thomas Strecker iD, Ariane Balaram iD, Peter Halfmann iD, Erica Ollmann Saphire iD, Daniel J. Lightwood iD, Alain R. Townsend, Simon J. Draper iD

Abstract

Ebolavirus disease (EVD) is caused by multiple species of Ebolavirus. Monoclonal antibodies (mAbs) against the virus glycoprotein (GP) are the only class of therapeutic approved for treatment of EVD caused by Zaire ebolavirus (EBOV). Therefore, mAbs targeting multiple Ebolavirus species may represent the next generation of EVD therapeutics. Broadly reactive anti-GP mAbs were produced; among these, mAbs 11886 and 11883 were broadly neutralizing in vitro. A 3.0 [A] cryo-electron microscopy structure of EBOV GP bound to both mAbs shows that 11886 binds a novel epitope bridging the glycan cap (GC), 310 pocket and GP2 N-terminus, whereas 11883 binds the receptor binding region (RBR) and GC. In vitro, 11886 synergized with a range of mAbs with epitope specificities spanning the RBR/GC, including 11883. Notably, 11886 increased the breadth of neutralization by partner mAbs against different Ebolavirus species. These data provide a strategic route to design improved mAb-based next-generation EVD therapeutics.

PDF DOI