| Literature DB >> 30629918 |
Zachary A Bornholdt1, Andrew S Herbert2, Chad E Mire3, Shihua He4, Robert W Cross3, Anna Z Wec5, Dafna M Abelson1, Joan B Geisbert3, Rebekah M James2, Md Niaz Rahim6, Wenjun Zhu4, Viktoriya Borisevich3, Logan Banadyga4, Bronwyn M Gunn7, Krystle N Agans3, Ariel S Wirchnianski5, Eileen Goodwin8, Kevin Tierney4, William S Shestowsky1, Ognian Bohorov1, Natasha Bohorova1, Jesus Velasco1, Eric Ailor1, Do Kim1, Michael H Pauly1, Kevin J Whaley1, Galit Alter7, Laura M Walker8, Kartik Chandran5, Larry Zeitlin9, Xiangguo Qiu10, Thomas W Geisbert11, John M Dye12.
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.Entities:
Keywords: ADI-15878; ADI-23774; BDBV; Bundibugyo; EBOV; MBP134; SUDV; Sudan; ebolavirus; pan-ebolavirus
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Year: 2019 PMID： 30629918 PMCID： PMC6341996 DOI： 10.1016/j.chom.2018.12.005
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023