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
- Journal volume & issue
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Vol. 43,
no. 7
p. 114502
Abstract
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.
