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Cell Host Microbe. 2019 Jan 9;25(1):49-58.e5. doi: 10.1016/j.chom.2018.12.005.

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

Author information

1
Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
2
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
3
Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
4
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
5
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
6
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
7
The Ragon Institute, Cambridge, MA, USA.
8
Adimab LLC, Lebanon, NH, USA.
9
Mapp Biopharmaceutical, Inc., San Diego, CA, USA. Electronic address: larry.zeitlin@mappbio.com.
10
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. Electronic address: xiangguo.qiu@canada.ca.
11
Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX, USA. Electronic address: twgeisbe@utmb.edu.
12
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA. Electronic address: john.m.dye1.civ@mail.mil.

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 MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134AF 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 MBP134AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.

KEYWORDS:

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

PMID:
30629918
PMCID:
PMC6341996
[Available on 2020-01-09]
DOI:
10.1016/j.chom.2018.12.005

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