Development of an antibody cocktail for treatment of Sudan virus infection.

Autor:	Herbert AS; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702.; The Geneva Foundation, Tacoma, WA 98402., Froude JW; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702., Ortiz RA; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702., Kuehne AI; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702., Dorosky DE; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702., Bakken RR; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702., Zak SE; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702.; The Geneva Foundation, Tacoma, WA 98402., Josleyn NM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702.; The Geneva Foundation, Tacoma, WA 98402., Musiychuk K; Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711., Jones RM; Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711., Green B; Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711., Streatfield SJ; Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711., Wec AZ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461., Bohorova N; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Bohorov O; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Kim DH; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Pauly MH; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Velasco J; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Whaley KJ; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Stonier SW; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702.; The Geneva Foundation, Tacoma, WA 98402., Bornholdt ZA; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461., Zeitlin L; Mapp Biopharmaceutical, Inc., San Diego, CA 92121., Sampey D; BioFactura, Inc., Frederick, MD 21701., Yusibov V; Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711., Dye JM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; john.m.dye1.civ@mail.mil.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Feb 18; Vol. 117 (7), pp. 3768-3778. Date of Electronic Publication: 2020 Feb 03.
DOI:	10.1073/pnas.1914985117
Abstrakt:	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. Competing Interests: Competing interest statement: The US Army Medical Research Institute of Infectious Disease (USAMRIID) has filed a patent application on the murine mAb 16F6 (WO2011071574 A2) entitled “Monoclonal Antibodies against Glycoprotein of Ebola Sudan Boniface Virus” with J.M.D. as a co-inventor. An invention disclosure entitled “Cross Reactive Antibodies to Ebola and Sudan Virus” has been filed for macaque mAbs X10B1, X10H2, X10F3, and X10B6 with A.S.H., J.W.F., and J.M.D. as co-inventors. N.B., O.B., D.H.K., M.H.P., and J.V. are employees of Mapp Bioparmaceutical, Inc. K.J.W. and L.Z. are employees and owners of Mapp Biopharmaceutical, Inc.
Databáze:	MEDLINE
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