Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.

Autor:	Shin OS; Adimab, LLC, Lebanon, NH 03766, USA., Monticelli SR; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; Geneva Foundation, Tacoma, WA 98042, USA., Hjorth CK; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA., Hornet V; Adimab, LLC, Lebanon, NH 03766, USA., Doyle M; Adimab, LLC, Lebanon, NH 03766, USA., Abelson D; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Kuehne AI; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Wang A; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Bakken RR; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Mishra AK; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA., Middlecamp M; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Champney E; Adimab, LLC, Lebanon, NH 03766, USA., Stuart L; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Maurer DP; Adimab, LLC, Lebanon, NH 03766, USA., Li J; Adimab, LLC, Lebanon, NH 03766, USA., Berrigan J; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Barajas J; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Balinandi S; Uganda Virus Research Institute, Entebbe, Uganda., Lutwama JJ; Uganda Virus Research Institute, Entebbe, Uganda., Lobel L; Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel., Zeitlin L; Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA., Walker LM; Adimab, LLC, Lebanon, NH 03766, USA., Dye JM; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. Electronic address: andrew.s.herbert4.civ@health.mil., Pauli NT; Adimab, LLC, Lebanon, NH 03766, USA. Electronic address: noel.pauli@adimab.com., McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: jmclellan@austin.utexas.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114502. Date of Electronic Publication: 2024 Jul 13.
DOI:	10.1016/j.celrep.2024.114502
Abstrakt:	Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics. Competing Interests: Declaration of interests E.C., J.L., and N.T.P. are employees and shareholders of Adimab, LLC. O.S.S., V.H., M.D., D.P.M., and L.M.W. are shareholders of Adimab. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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