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Development of an antibody cocktail for treatment of Sudan virus infection

 
: Herbert, A.S.; Froude, J.W.; Ortiz, R.A.; Kuehne, A.I.; Dorosky, D.E.; Bakken, R.R.; Zak, S.E.; Josleyn, N.M.; Musiychuk, K.; Mark Jones, R.; Green, B.; Streatfield, S.J.; Wec, A.Z.; Bohorova, N.; Bohorov, O.; Kim, D.H.; Pauly, M.H.; Velasco, J.; Whaley, K.J.; Stonier, S.W.; Bornholdt, Z.A.; Chandran, K.; Zeitlin, L.; Sampey, D.; Yusibov, V.; Dye, J.M.

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Proceedings of the National Academy of Sciences of the United States of America : PNAS 117 (2020), No.7, pp.3768-3778
ISSN: 0027-8424
ISSN: 1091-6490
English
Journal Article
Fraunhofer CMB ()

Abstract
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.

: http://publica.fraunhofer.de/documents/N-582357.html