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 Bohorov; Natasha 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

doi:10.1016/j.chom.2018.12.005

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

Microbiology And Immunology

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

30 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 language	English (US)
Pages (from-to)	49-58.e5
Journal	Cell Host and Microbe
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2018.12.005
State	Published - 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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10.1016/j.chom.2018.12.005

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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

Bornholdt, ZA, Herbert, AS, Mire, CE, He, S, Cross, RW, Wec, AZ, Abelson, DM, Geisbert, JB, James, RM, Rahim, MN, Zhu, W, Borisevich, V, Banadyga, L, Gunn, BM, Agans, KN, Wirchnianski, AS, Goodwin, E, Tierney, K, Shestowsky, WS, Bohorov, O, Bohorova, N, Velasco, J, Ailor, E, Kim, D, Pauly, MH, Whaley, KJ, Alter, G, Walker, LM, Chandran, K, Zeitlin, L, Qiu, X, Geisbert, TW & Dye, JM 2019, 'A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates', Cell Host and Microbe, vol. 25, no. 1, pp. 49-58.e5. https://doi.org/10.1016/j.chom.2018.12.005

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

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.",

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AU - He, Shihua

AU - Cross, Robert W.

AU - Wec, Anna Z.

AU - Abelson, Dafna M.

AU - Geisbert, Joan B.

AU - James, Rebekah M.

AU - Rahim, Md Niaz

AU - Zhu, Wenjun

AU - Borisevich, Viktoriya

AU - Banadyga, Logan

AU - Gunn, Bronwyn M.

AU - Agans, Krystle N.

AU - Wirchnianski, Ariel S.

AU - Goodwin, Eileen

AU - Tierney, Kevin

AU - Shestowsky, William S.

AU - Bohorov, Ognian

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AU - Velasco, Jesus

AU - Ailor, Eric

AU - Kim, Do

AU - Pauly, Michael H.

AU - Whaley, Kevin J.

AU - Alter, Galit

AU - Walker, Laura M.

AU - Chandran, Kartik

AU - Zeitlin, Larry

AU - Qiu, Xiangguo

AU - Geisbert, Thomas W.

AU - Dye, John M.

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N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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