Cell host & microbe · 2019
A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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Bornholdt Zachary A, Herbert Andrew S, Mire Chad E, He Shihua, Cross Robert W, Wec Anna Z, Abelson Dafna M, Geisbert Joan B, James Rebekah M, Rahim Md Niaz, Zhu Wenjun, Borisevich Viktoriya, Banadyga Logan, Gunn Bronwyn M, Agans Krystle N, Wirchnianski Ariel S, Goodwin Eileen, Tierney Kevin, Shestowsky William S, Bohorov Ognian, Bohorova Natasha, Velasco Jesus, Ailor Eric, Kim Do, Pauly Michael H, Whaley Kevin J, Alter Galit, Walker Laura M, Chandran Kartik, Zeitlin Larry, Qiu Xiangguo, Geisbert Thomas W, Dye John M
Аннотация
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.
Предметные рубрики MeSH
Animal WelfareAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCell LineChlorocebus aethiopsDisease Models, AnimalEbolavirusFemaleFerretsFiloviridaeFiloviridae InfectionsGlycoproteinsGuinea PigsHEK293 CellsHemorrhagic Fever, EbolaHumansKiller Cells, NaturalMacacaMacaca fascicularisMalePrimatesSurvival AnalysisTreatment OutcomeViral Proteins