Cell Reports
(Jul 2024)
Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38
Olivia S. Shin,
Stephanie R. Monticelli,
Christy K. Hjorth,
Vladlena Hornet,
Michael Doyle,
Dafna Abelson,
Ana I. Kuehne,
Albert Wang,
Russell R. Bakken,
Akaash K. Mishra,
Marissa Middlecamp,
Elizabeth Champney,
Lauran Stuart,
Daniel P. Maurer,
Jiannan Li,
Jacob Berrigan,
Jennifer Barajas,
Stephen Balinandi,
Julius J. Lutwama,
Leslie Lobel,
Larry Zeitlin,
Laura M. Walker,
John M. Dye,
Kartik Chandran,
Andrew S. Herbert,
Noel T. Pauli,
Jason S. McLellan
Affiliations
Olivia S. Shin
Adimab, LLC, Lebanon, NH 03766, USA
Stephanie R. Monticelli
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; Geneva Foundation, Tacoma, WA 98042, USA
Christy K. Hjorth
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Vladlena Hornet
Adimab, LLC, Lebanon, NH 03766, USA
Michael Doyle
Adimab, LLC, Lebanon, NH 03766, USA
Dafna Abelson
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA
Ana I. Kuehne
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Albert Wang
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Russell R. Bakken
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Akaash K. Mishra
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Marissa Middlecamp
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA
Elizabeth Champney
Adimab, LLC, Lebanon, NH 03766, USA
Lauran Stuart
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA
Daniel P. Maurer
Adimab, LLC, Lebanon, NH 03766, USA
Jiannan Li
Adimab, LLC, Lebanon, NH 03766, USA
Jacob Berrigan
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Jennifer Barajas
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA
Stephen Balinandi
Uganda Virus Research Institute, Entebbe, Uganda
Julius J. Lutwama
Uganda Virus Research Institute, Entebbe, Uganda
Leslie Lobel
Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Larry Zeitlin
Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA
Laura M. Walker
Adimab, LLC, Lebanon, NH 03766, USA
John M. Dye
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Kartik Chandran
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Andrew S. Herbert
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; Corresponding author
Noel T. Pauli
Adimab, LLC, Lebanon, NH 03766, USA; Corresponding author
Jason S. McLellan
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA; Corresponding author
DOI
https://doi.org/10.1016/j.celrep.2024.114502
Journal volume & issue
Vol. 43,
no. 7
Abstract
Read online
Summary: 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.
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