Development of an antibody cocktail for treatment of Sudan virus infection

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 7; pp. 3768 - 3778
• Main Authors: Herbert, Andrew S., Froude, Jeffery W., Ortiz, Ramon A., Kuehne, Ana I., Dorosky, Danielle E., Bakken, Russell R., Zak, Samantha E., Josleyn, Nicole M., Musiychuk, Konstantin, Jones, R. Mark, Green, Brian, Streatfield, Stephen J., Wec, Anna Z., Bohorova, Natasha, Bohorov, Ognian, Kim, Do H., Pauly, Michael H., Velasco, Jesus, Whaley, Kevin J., Stonier, Spencer W., Bornholdt, Zachary A., Chandran, Kartik, Zeitlin, Larry, Sampey, Darryl, Yusibov, Vidadi, Dye, John M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.02.2020
• Subjects: Binding; Biological Sciences; Epitopes; Evaluation; Glycan; Glycoproteins; In vivo methods and tests; Infections; Mammals; Monoclonal antibodies; Mucin; Neutralizers; Therapeutic applications; Viruses; Sudan; Sudan virus; ebolavirus; monoclonal antibody; cocktail; therapy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1914985117

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.