1. Academic Validation
  2. Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets

Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets

  • Antiviral Res. 2018 Aug:156:64-71. doi: 10.1016/j.antiviral.2018.06.006.
Emmie de Wit 1 Friederike Feldmann 2 Atsushi Okumura 3 Eva Horne 4 Elaine Haddock 4 Greg Saturday 2 Dana Scott 2 Karl J Erlandson 5 Neil Stahl 6 Leah Lipsich 6 Christos A Kyratsous 6 Heinz Feldmann 4
Affiliations

Affiliations

  • 1 Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. Electronic address: emmie.dewit@nih.gov.
  • 2 Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
  • 3 Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • 4 Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
  • 5 Biomedical Advanced Research and Development Authority, Washington, DC, USA.
  • 6 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Abstract

The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV Infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When Animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in Animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated Animals developed bronchointerstitial pneumonia of similar severity as the control Animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.

Keywords

Animal model; Common marmoset; MERS-CoV; Monoclonal antibody treatment; Neutralizing antibody.

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