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; Thomas W. Geisbert

doi:10.1038/s41467-021-22132-0

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, Thomas W. Geisbert

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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.

Original language	English (US)
Article number	1891
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22132-0
State	Published - Dec 1 2021

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Cross, R. W., Bornholdt, Z. A., Prasad, A. N., Borisevich, V., Agans, K. N., Deer, D. J., Abelson, D. M., Kim, D. H., Shestowsky, W. S., Campbell, L. A., Bunyan, E., Geisbert, J. B., Fenton, K. A., Zeitlin, L., Porter, D. P., & Geisbert, T. W. (2021). Combination therapy protects macaques against advanced Marburg virus disease. Nature communications, 12(1), Article 1891. https://doi.org/10.1038/s41467-021-22132-0

Cross, RW, Bornholdt, ZA, Prasad, AN, Borisevich, V, Agans, KN, Deer, DJ, Abelson, DM, Kim, DH, Shestowsky, WS, Campbell, LA, Bunyan, E, Geisbert, JB, Fenton, KA, Zeitlin, L, Porter, DP & Geisbert, TW 2021, 'Combination therapy protects macaques against advanced Marburg virus disease', Nature communications, vol. 12, no. 1, 1891. https://doi.org/10.1038/s41467-021-22132-0

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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.",

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Combination therapy protects macaques against advanced Marburg virus disease

Abstract

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