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

Antiviral Res. 2016 Aug:132:141-8. doi: 10.1016/j.antiviral.2016.06.003. Epub 2016 Jun 14.

Abstract

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology*
  • Cell Line
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / mortality
  • Coronavirus Infections / virology*
  • Cross Reactions / immunology
  • Dipeptidyl Peptidase 4 / metabolism
  • Disease Models, Animal
  • Epitopes / immunology
  • Female
  • Humans
  • Mice
  • Mice, Transgenic
  • Middle East Respiratory Syndrome Coronavirus / drug effects
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Neutralization Tests
  • Protein Binding
  • Receptors, Virus / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Receptors, Virus
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4