A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates

Zachary A. Bornholdt, Andrew S. Herbert, Chad E. Mire, Shihua He, Robert W. Cross, Anna Z. Wec, Dafna M. Abelson, Joan B. Geisbert, Rebekah M. James, Md Niaz Rahim, Wenjun Zhu, Viktoriya Borisevich, Logan Banadyga, Bronwyn M. Gunn, Krystle N. Agans, Ariel S. Wirchnianski, Eileen Goodwin, Kevin Tierney, William S. Shestowsky, Ognian BohorovNatasha Bohorova, Jesus Velasco, Eric Ailor, Do Kim, Michael H. Pauly, Kevin J. Whaley, Galit Alter, Laura M. Walker, Kartik Chandran, Larry Zeitlin, Xiangguo Qiu, Thomas W. Geisbert, John M. Dye

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134 AF , a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134 AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134 AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.

Original languageEnglish (US)
Pages (from-to)49-58.e5
JournalCell Host and Microbe
Volume25
Issue number1
DOIs
StatePublished - Jan 9 2019

Keywords

  • ADI-15878
  • ADI-23774
  • BDBV
  • Bundibugyo
  • EBOV
  • MBP134
  • SUDV
  • Sudan
  • ebolavirus
  • pan-ebolavirus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Bornholdt, Z. A., Herbert, A. S., Mire, C. E., He, S., Cross, R. W., Wec, A. Z., Abelson, D. M., Geisbert, J. B., James, R. M., Rahim, M. N., Zhu, W., Borisevich, V., Banadyga, L., Gunn, B. M., Agans, K. N., Wirchnianski, A. S., Goodwin, E., Tierney, K., Shestowsky, W. S., ... Dye, J. M. (2019). A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates. Cell Host and Microbe, 25(1), 49-58.e5. https://doi.org/10.1016/j.chom.2018.12.005