Development of a Human Antibody Cocktail to protects animals from three deadly Ebola viruses

Scientists have developed a combination of monoclonal antibodies that protected animals from all three Ebola viruses that cause human disease. The antibody 'cocktail,' called MBP134, is the first experimental treatment to protect monkeys against Ebola virus (formerly known as Ebola Zaire), as well as Sudan virus and Bundibugyo virus, and could lead to a broadly effective therapeutic

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Summary:Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, research in advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. 

MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.

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Journal References:

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1. 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. A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates. Cell Host & Microbe, 2019; 25 (1): 49