Details

Autor(en) / Beteiligte

• Chapman, Nathaniel S
• Hulswit, Ruben J G
• Westover, Jonna L B
• Stass, Robert
• Paesen, Guido C
• Binshtein, Elad
• Reidy, Joseph X
• Engdahl, Taylor B
• Handal, Laura S
• Flores, Alejandra
• Gowen, Brian B
• Bowden, Thomas A
• Crowe, Jr, James E

Titel

Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses

Ist Teil von

• Nature communications, 2023-09, Vol.14 (1), p.5650-5650, Article 5650

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.