Maftivimab monotherapy is effective in a non-human primate model of Bundibugyo virus disease
Year: 2026
Type: preprint
Abstract: The 2026 outbreak of Bundibugyo ebolavirus (BDBV) in the Democratic Republic of the Congo and Uganda has created an urgent need for treatments for BDBV disease, yet the only FDA-approved ebolavirus therapeutics, the monoclonal antibody (mAb) cocktail Inmazeb® and the mAb Ebanga®, are indicated for Zaire ebolavirus (EBOV). Maftivimab (REGN3479), the most potent neutralizing component of Inmazeb®, targets ebolavirus species GPs broadly; however, how it engages BDBV GP, whether it neutralizes BDBV-2026, and whether it protects against BDBV disease in vivo are unknown. Here we show that Maftivimab binds to BDBV-2007 GP with high affinity and potently neutralizes pseudoviruses carrying GP from a 2007 reference strain and the 2026 outbreak lineage. Additionally, a cryo-electron microscopy structure of Maftivimab Fab bound to trimeric BDBV-2007 GP superimposes closely on the EBOV GP–Maftivimab complex; importantly, all GP contact residues are conserved between the 2007 and 2026 BDBV sequences. Finally, in cynomolgus macaques challenged with BDBV-2007, a single dose of Maftivimab monotherapy given 7 days after infection, after the onset of clinical disease, rescued 6 of 6 animals, whereas 5 of 6 placebo-treated animals succumbed. These findings demonstrate that Maftivimab neutralizes BDBV, binds to its epitope on BDBV GP and is efficacious in treating established BDBV disease in the macaque model. The data support its evaluation in clinical trials during the ongoing or future outbreak.
Authors: Meike Dittmann, Dylan M. Johnson, Micah Rapp, Alida Coppi, Flonza Isa, Dharani Ajithdoss, Anbo Zhou, Benjamin O. Fulton, Ranu Basu, Anna K. Kania, Kristen E. Pascal, Robert LeDesma, George Ehrlich, Ashique Rafique, Victoria Marzec, Jiacheng Yuan, Ruiqi Liu, Kendra Alfson, Tessa Moir-Savitz, Stanton Gray, Greg Ippolito, Cory Hallam, Jean Patterson, Alina Baum, Veronica Mas Casullo, Richard Copin, Viraj Kulkarni, Matthew C. Franklin, Christos A. Kyratsous, Jamie M. Orengo
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221767055