Discovery of potent cross-neutralizing antibodies for the treatment of Marburg virus disease

Abstract Marburg virus (MARV) and Ravn virus (RAVV) are highly pathogenic filoviruses that cause Marburg virus disease (MVD), for which no approved treatment currently exists. In this study, we describe a panel of 10 novel mouse-derived monoclonal antibodies (mAbs), all exhibiting neutralizing activity against MARV. Notably, five of these mAbs also cross-neutralize RAVV. Based on amino acid sequences, neutralization profiles, and escape mutations in the MARV glycoprotein (GP), the mAbs were classified into three groups. mAbs targeting the receptor-binding domain (RBD) and mucin-like domain exhibited MARV-specific neutralization, whereas those targeting epitopes spanning the RBD and internal fusion loop exhibited cross-neutralization. Post-exposure administration of cross-neutralizing mAbs (AGP-R7, AGP-R12) provided significant protection in MARV and RAVV infection mouse models. These findings identify a conserved neutralizing epitope with therapeutic potential and highlight AGP-R7 and AGP-R12 as promising candidates for MVD treatment. This study offers new insights into cross-reactive antibody strategies against multiple filoviruses.