4.7 Article

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

Journal

ANTIVIRAL RESEARCH
Volume 132, Issue -, Pages 141-148

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2016.06.003

Keywords

MERS-CoV; Receptor-binding domain; Humanized monoclonal antibody; Protection; Treatment; Lethal infection

Funding

  1. China National Program of Infectious Disease fund [2014ZX10004001004]
  2. NIH [R21AI109094]
  3. intramural fund of the New York Blood Center [NYB000348]

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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. (C) 2016 The Authors. Published by Elsevier B.V.

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