Combination therapy protects macaques against advanced Marburg virus disease

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, Elaine Bunyan, Joan B. Geisbert, Karla A. Fenton, Larry Zeitlin (), Danielle P. Porter () and Thomas W. Geisbert ()
Additional contact information
Robert W. Cross: University of Texas Medical Branch
Zachary A. Bornholdt: Mapp Biopharmaceutical, Inc.
Abhishek N. Prasad: University of Texas Medical Branch
Viktoriya Borisevich: University of Texas Medical Branch
Krystle N. Agans: University of Texas Medical Branch
Daniel J. Deer: 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
Karla A. Fenton: University of Texas Medical Branch
Larry Zeitlin: Mapp Biopharmaceutical, Inc.
Danielle P. Porter: Gilead Sciences, Inc.
Thomas W. Geisbert: University of Texas Medical Branch

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22132-0

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