| Literature DB >> 30629917 |
Anna Z Wec1, Zachary A Bornholdt2, Shihua He3, Andrew S Herbert4, Eileen Goodwin5, Ariel S Wirchnianski1, Bronwyn M Gunn6, Zirui Zhang7, Wenjun Zhu7, Guodong Liu7, Dafna M Abelson2, Crystal L Moyer2, Rohit K Jangra1, Rebekah M James4, Russell R Bakken4, Natasha Bohorova2, Ognian Bohorov2, Do H Kim2, Michael H Pauly2, Jesus Velasco2, Robert H Bortz1, Kevin J Whaley2, Tracey Goldstein8, Simon J Anthony9, Galit Alter6, Laura M Walker5, John M Dye4, Larry Zeitlin10, Xiangguo Qiu11, Kartik Chandran12.
Abstract
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, we 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.Entities:
Keywords: Ebola glycoprotein; Ebola virus; antibody cocktail; antibody engineering; antiviral drug; broadly neutralizing antibodies; ebolavirus; filovirus; human monoclonal antibodies; immunotherapy
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Year: 2019 PMID： 30629917 PMCID： PMC6396299 DOI： 10.1016/j.chom.2018.12.004
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023