Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates
| العنوان: | Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates |
|---|---|
| المؤلفون: | Andrew B. Ward, Christos A. Kyratsous, Ricardo Carrion, Gabriella Worwa, William D. Pratt, Gang Chen, William C. Olson, Terra Potocky, Joel H. Martin, Karl J. Erlandson, John C. Trefry, Ashique Rafique, Peter W. Mason, Hilary M. Staples, Tammy T. Huang, Hannah L. Turner, Robert Babb, Drew Dudgeon, Leah Lipsich, Joshua D. Shamblin, Ying Yan, Yasuteru Sakurai, Thomas M Dreier, Manu Anantpadma, Kevin Yu, Marcela Torres, Sandra L. Bixler, Suzanne E. Wollen, Charles D. Murin, Neil Stahl, Justine M. Zelko, Melissa S Willis, Robert A. Davey, Darya Burakov, Jeanette L. Fairhurst, Ashok Badithe, Margaret L. Pitt, Franco Rossi, Taylor B. Chance, Kimberly Armstrong, Kristen E. Pascal |
| المصدر: | The Journal of Infectious Diseases |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, filovirus, medicine.drug_class, Guinea Pigs, Supplement Articles, Disease, medicine.disease_cause, Monoclonal antibody, Antibodies, Viral, 03 medical and health sciences, Mice, 0302 clinical medicine, Emerging infections, Medicine, Animals, Humans, Immunology and Allergy, Glycoproteins, Ebola virus, biology, business.industry, Antibodies, Monoclonal, Binding (Molecular Function), Hemorrhagic Fever, Ebola, Virology, Antibodies, Neutralizing, Macaca mulatta, Treatment, 030104 developmental biology, HEK293 Cells, Infectious Diseases, biology.protein, monoclonal antibodies, Antibody, business, 030217 neurology & neurosurgery, EBOV |
| الوصف: | 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 FcγRIIIa. 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. |
| تدمد: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiy285 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48fdd30e7fa7a70f592379ed4387a859 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....48fdd30e7fa7a70f592379ed4387a859 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376613 00221899 |
|---|---|
| DOI: | 10.1093/infdis/jiy285 |