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Combination therapy protects macaques against advanced Marburg virus disease

Author

Listed:
  • Robert W. Cross

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Zachary A. Bornholdt

    (Mapp Biopharmaceutical, Inc.)

  • Abhishek N. Prasad

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Viktoriya Borisevich

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Krystle N. Agans

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Daniel J. Deer

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Dafna M. Abelson

    (Mapp Biopharmaceutical, Inc.)

  • Do H. Kim

    (Mapp Biopharmaceutical, Inc.)

  • William S. Shestowsky

    (Mapp Biopharmaceutical, Inc.)

  • Lioudmila A. Campbell

    (Mapp Biopharmaceutical, Inc.)

  • Elaine Bunyan

    (Gilead Sciences, Inc.)

  • Joan B. Geisbert

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Karla A. Fenton

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Larry Zeitlin

    (Mapp Biopharmaceutical, Inc.)

  • Danielle P. Porter

    (Gilead Sciences, Inc.)

  • Thomas W. Geisbert

    (University of Texas Medical Branch
    University of Texas Medical Branch)

Abstract

Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

Suggested Citation

  • Robert W. Cross & Zachary A. Bornholdt & Abhishek N. Prasad & Viktoriya Borisevich & Krystle N. Agans & Daniel J. Deer & Dafna M. Abelson & Do H. Kim & William S. Shestowsky & Lioudmila A. Campbell & , 2021. "Combination therapy protects macaques against advanced Marburg virus disease," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22132-0
    DOI: 10.1038/s41467-021-22132-0
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    Cited by:

    1. Surender Khurana & Gabrielle Grubbs & Supriya Ravichandran & Emily Cluff & JungHyun Kim & Ana I. Kuehne & Samantha Zak & John M. Dye & Julius J. Lutwama & Andrew S. Herbert, 2024. "Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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