Journal article
Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates
The Journal of infectious diseases, Vol.218(5), pp.S612-S626
12/15/2018
DOI: 10.1093/infdis/jiy285
PMCID: PMC6249601
PMID: 29860496
Abstract
Background For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.
Methods In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses.
Results Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent.
Conclusions This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.
Details
- Title: Subtitle
- Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates
- Creators
- Kristen E. Pascal - Regeneron (United States)Drew Dudgeon - Regeneron (United States)John C. Trefry - United States Army Medical Research Institute of Infectious DiseasesManu Anantpadma - Texas Biomedical Research InstituteYasuteru Sakurai - Texas Biomedical Research InstituteCharles D. Murin - Scripps Research InstituteHannah L. Turner - Scripps Research InstituteJeanette Fairhurst - Regeneron (United States)Marcela Torres - Regeneron (United States)Ashique Rafique - Regeneron (United States)Ying Yan - Regeneron (United States)Ashok Badithe - Regeneron (United States)Kevin Yu - Regeneron (United States)Terra Potocky - Regeneron (United States)Sandra L. Bixler - United States Army Medical Research Institute of Infectious DiseasesTaylor B. Chance - United States Army Medical Research Institute of Infectious DiseasesWilliam D. Pratt - United States Army Medical Research Institute of Infectious DiseasesFranco D. Rossi - United States Army Medical Research Institute of Infectious DiseasesJoshua D. Shamblin - United States Army Medical Research Institute of Infectious DiseasesSuzanne E. Wollen - United States Army Medical Research Institute of Infectious DiseasesJustine M. Zelko - United States Army Medical Research Institute of Infectious DiseasesRicardo Carrion - Texas Biomedical Research InstituteGabriella Worwa - Texas Biomedical Research InstituteHilary M. Staples - Texas Biomedical Research InstituteDarya Burakov - Regeneron (United States)Robert Babb - Regeneron (United States)Gang Chen - Regeneron (United States)Joel Martin - Regeneron (United States)Tammy T. Huang - Regeneron (United States)Karl Erlandson - United States Department of Health and Human ServicesMelissa S. Willis - United States Department of Health and Human ServicesKimberly Armstrong - United States Department of Health and Human ServicesThomas M. Dreier - United States Department of Health and Human ServicesAndrew B. Ward - Scripps Research InstituteRobert A. Davey - Regeneron (United States)Margaret L. M. Pitt - United States Army Medical Research Institute of Infectious DiseasesLeah Lipsich - Regeneron (United States)Peter Mason - Regeneron (United States)William Olson - Regeneron (United States)Neil Stahl - Regeneron (United States)Christos A. Kyratsous - Regeneron (United States)
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.218(5), pp.S612-S626
- DOI
- 10.1093/infdis/jiy285
- PMID
- 29860496
- PMCID
- PMC6249601
- NLM abbreviation
- J Infect Dis
- ISSN
- 0022-1899
- eISSN
- 1537-6613
- Publisher
- Oxford Univ Press
- Number of pages
- 15
- Grant note
- Department of Health and Human Services Regeneron Pharmaceuticals, Inc.; Regeneron BARDA HHSO100201500013C / Biomedical Advanced Research and Development Authority (BARDA) Office of the Assistant Secretary for Preparedness and Response P51OD011133 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/15/2018
- Academic Unit
- Dermatology
- Record Identifier
- 9984296215502771
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