Development of an antibody cocktail for treatment of Sudan virus infection
| Autor: | Ramon A. Ortiz, Natasha Bohorova, Anna Z. Wec, Darryl Sampey, Kartik Chandran, Nicole M. Josleyn, Stephen J. Streatfield, Jeffery W. Froude, Ognian Bohorov, Samantha E. Zak, Zachary A. Bornholdt, Russell R. Bakken, R. Mark Jones, Andrew S. Herbert, Brian J. Green, Larry Zeitlin, Ana I. Kuehne, Do Han Kim, Spencer W. Stonier, Kevin J. Whaley, Danielle E. Dorosky, Michael H. Pauly, John M. Dye, Jesus Velasco, Vidadi Yusibov, Konstantin Musiychuk |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Glycan medicine.drug_class Biology Antibodies Viral medicine.disease_cause Monoclonal antibody Virus Mice Viral Proteins 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals Humans 030212 general & internal medicine Glycoproteins Ebolavirus Multidisciplinary Ebola virus Antibodies Monoclonal Hemorrhagic Fever Ebola Biological Sciences Macaca mulatta Virology In vitro Disease Models Animal 030104 developmental biology biology.protein Female Immunotherapy Antibody |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection. |
| Databáze: | OpenAIRE |
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