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Cell Host Microbe. 2019 Jan 9;25(1):39-48.e5. doi: 10.1016/j.chom.2018.12.004.

Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection.

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Mapp Biopharmaceutical, San Diego, CA 92121, USA.
3
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
4
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
5
Adimab, LLC, Lebanon, NH 03766, USA.
6
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
7
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
8
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
9
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
10
Mapp Biopharmaceutical, San Diego, CA 92121, USA. Electronic address: larry.zeitlin@mappbio.com.
11
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Electronic address: xiangguo.qiu@canada.ca.
12
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: kartik.chandran@einstein.yu.edu.

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.

KEYWORDS:

Ebola glycoprotein; Ebola virus; antibody cocktail; antibody engineering; antiviral drug; broadly neutralizing antibodies; ebolavirus; filovirus; human monoclonal antibodies; immunotherapy

PMID:
30629917
DOI:
10.1016/j.chom.2018.12.004

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