Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

- A humanized monoclonal antibody (mAb) against Middle East respiratory syndrome coronavirus (MERS-CoV), hMS-1, was generated.
- hMS-1 bound to the MERS-CoV receptor binding domain (RBD) with high affinity.
- hMS-1 neutralized MERS-CoV infection by blocking the binding of MERS-CoV RBD to the hDPP4 receptor.
- Humanized mAb hMS-1 recognized conserved RBD epitopes and cross-neutralized MERS-CoV evolved strains.
- Single-dose treatment of mAb hMS-1 provided full protection from lethal MERS-CoV infection in an hDPP4-Tg mouse model.

Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.