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

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. 25:49-58.e5.

[doi: 10.1016/j.chom.2018.12.005]  [Download PDF]


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.