دورية أكاديمية
أعرض في EDS

Protective neutralizing antibodies from human survivors of Crimean-Congo hemorrhagic fever.

التفاصيل البيبلوغرافية
العنوان: Protective neutralizing antibodies from human survivors of Crimean-Congo hemorrhagic fever.
المؤلفون: Fels JM; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Maurer DP; Adimab, LLC, Lebanon, NH 03766, USA., Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; The Geneva Foundation, Tacoma, WA 98402, USA., Wirchnianski AS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Vergnolle O; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Cross RW; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA., Abelson DM; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Moyer CL; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Mishra AK; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Aguilan JT; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Kuehne AI; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Pauli NT; Adimab, LLC, Lebanon, NH 03766, USA., Bakken RR; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Nyakatura EK; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Hellert J; Structural Virology Unit, Department of Virology, CNRS UMR 3569, Institut Pasteur, Paris 75724, France., Quevedo G; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Lobel L; Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel., Balinandi S; Uganda Virus Research Institute, Entebbe, Uganda., Lutwama JJ; Uganda Virus Research Institute, Entebbe, Uganda., Zeitlin L; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Geisbert TW; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA., Rey FA; Structural Virology Unit, Department of Virology, CNRS UMR 3569, Institut Pasteur, Paris 75724, France., Sidoli S; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., McLellan JS; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Lai JR; Deparment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Bornholdt ZA; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA. Electronic address: zachary.bornholdt@mappbio.com., Dye JM; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. Electronic address: john.m.dye1.civ@mail.mil., Walker LM; Adimab, LLC, Lebanon, NH 03766, USA; Adagio Therapeutics, Inc., Waltham, MA 02451, USA. Electronic address: laura.walker@adimab.com., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: kartik.chandran@einsteinmed.org.
المصدر: Cell [Cell] 2021 Jun 24; Vol. 184 (13), pp. 3486-3501.e21. Date of Electronic Publication: 2021 Jun 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, Ma : Cell Press
Original Publication: Cambridge, MIT Press.
مواضيع طبية MeSH: Survivors*, Antibodies, Neutralizing/*immunology , Hemorrhagic Fever, Crimean/*immunology, Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/immunology ; Antigens, Viral/metabolism ; Biophysical Phenomena ; Chlorocebus aethiops ; Epitope Mapping ; Epitopes/metabolism ; Female ; Hemorrhagic Fever Virus, Crimean-Congo/immunology ; Hemorrhagic Fever, Crimean/prevention & control ; Humans ; Immunoglobulin G/metabolism ; Male ; Mice ; Neutralization Tests ; Protein Binding ; Protein Engineering ; Recombinant Proteins/immunology ; Vero Cells ; Viral Proteins/chemistry
مستخلص: Crimean-Congo hemorrhagic fever virus (CCHFV) is a World Health Organization priority pathogen. CCHFV infections cause a highly lethal hemorrhagic fever for which specific treatments and vaccines are urgently needed. Here, we characterize the human immune response to natural CCHFV infection to identify potent neutralizing monoclonal antibodies (nAbs) targeting the viral glycoprotein. Competition experiments showed that these nAbs bind six distinct antigenic sites in the Gc subunit. These sites were further delineated through mutagenesis and mapped onto a prefusion model of Gc. Pairwise screening identified combinations of non-competing nAbs that afford synergistic neutralization. Further enhancements in neutralization breadth and potency were attained by physically linking variable domains of synergistic nAb pairs through bispecific antibody (bsAb) engineering. Although multiple nAbs protected mice from lethal CCHFV challenge in pre- or post-exposure prophylactic settings, only a single bsAb, DVD-121-801, afforded therapeutic protection. DVD-121-801 is a promising candidate suitable for clinical development as a CCHFV therapeutic.
Competing Interests: Declaration of interests K.C. is a scientific advisory board member of Integrum Scientific and Biovaxys Technology Corporation. K.C., J.S.M., and J.R.L. are scientific advisory board members of the Pandemic Security Initiative of Celdara Medical. N.T.P. and L.M.W. are employees and shareholders of Adimab. D.P.M. is a shareholder of Adimab. Z.A.B., D.M.A., C.L.M., and L.Z. are shareholders and employees of Mapp Biopharmaceutical. Mapp Biopharmaceutical has filed a patent application related to this work.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 AI132246 United States AI NIAID NIH HHS; T32 AI070117 United States AI NIAID NIH HHS; U19 AI142777 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: CCHFV; Crimean-Congo hemorrhagic fever virus; antibody therapeutic; bunyavirus; emerging virus; human monoclonal antibody; monoclonal antibody; nairovirus; tickborne; viral glycoprotein
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Neutralizing)
0 (Antigens, Viral)
0 (Epitopes)
0 (Immunoglobulin G)
0 (Recombinant Proteins)
0 (Viral Proteins)
تواريخ الأحداث: Date Created: 20210602 Date Completed: 20220105 Latest Revision: 20220716
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8559771
DOI: 10.1016/j.cell.2021.05.001
PMID: 34077751
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4172
DOI:10.1016/j.cell.2021.05.001