TY - JOUR
T1 - Discovery of potent cross-neutralizing antibodies against Marburg and Ravn viruses with therapeutic potential
AU - Saito, Takeshi
AU - Miyamoto, Hiroko
AU - Igarashi, Manabu
AU - Nanbo, Asuka
AU - Hayashi, Risa
AU - Paroha, Ruchi
AU - Siman-Tov, Gavriella
AU - Littlefield, Kirsten
AU - Mori-Kajihara, Akina
AU - Click, Christine
AU - Furuyama, Wakako
AU - Paessler, Slobodan
AU - Maruyama, Junki
AU - Takada, Ayato
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105026279870
UR - https://www.scopus.com/pages/publications/105026279870#tab=citedBy
U2 - 10.1038/s44298-025-00168-z
DO - 10.1038/s44298-025-00168-z
M3 - Article
C2 - 41455801
AN - SCOPUS:105026279870
SN - 2948-1767
VL - 3
JO - NPJ Viruses
JF - NPJ Viruses
IS - 1
M1 - 84
ER -