Herbert, A.S.A.S.HerbertFroude, J.W.J.W.FroudeOrtiz, R.A.R.A.OrtizKuehne, A.I.A.I.KuehneDorosky, D.E.D.E.DoroskyBakken, R.R.R.R.BakkenZak, S.E.S.E.ZakJosleyn, N.M.N.M.JosleynMusiychuk, K.K.MusiychukMark Jones, R.R.Mark JonesGreen, B.B.GreenStreatfield, S.J.S.J.StreatfieldWec, A.Z.A.Z.WecBohorova, N.N.BohorovaBohorov, O.O.BohorovKim, D.H.D.H.KimPauly, M.H.M.H.PaulyVelasco, J.J.VelascoWhaley, K.J.K.J.WhaleyStonier, S.W.S.W.StonierBornholdt, Z.A.Z.A.BornholdtChandran, K.K.ChandranZeitlin, L.L.ZeitlinSampey, D.D.SampeyYusibov, V.V.YusibovDye, J.M.J.M.Dye2022-03-062022-03-062020https://publica.fraunhofer.de/handle/publica/26289010.1073/pnas.19149851172-s2.0-85079531798Antibody-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.en505journal article