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Human antibody reco...
Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
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- Mittler, Eva (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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- Wec, Anna Z. (author)
- Adimab, LLC, United States
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- Tynell, Janne (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi,Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
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- Guardado-Calvo, Pablo (author)
- Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
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- Wigren, Julia (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Polanco, Laura C. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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- O'Brien, Cecilia M. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA
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- Slough, Megan M. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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- Abelson, Dafna M. (author)
- Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
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- Serris, Alexandra (author)
- Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
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- Sakharkar, Mrunal (author)
- Adimab, LLC, United States
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- Pehau-Arnaudet, Gerard (author)
- Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
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- Bakken, Russell R. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States
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- Geoghegan, James C. (author)
- Adimab, LLC, United States
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- Jangra, Rohit K. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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- Keller, Markus (author)
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
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- Zeitlin, Larry (author)
- Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
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- Vapalahti, Olli (author)
- Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland; Veterinary Biosciences, Veterinary Faculty, University of Helsinki, Helsinki, Finland
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- Ulrich, Rainer G. (author)
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; Deutsches Zentrum für Infektionsforschung, Partner site Hamburg-Lübeck- Borstel-Riems, Greifswald-Insel Riems, Germany
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- Bornholdt, Zachary A. (author)
- Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
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- Ahlm, Clas, 1956- (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Rey, Felix A. (author)
- Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
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- Dye, John M. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States
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- Bradfute, Steven B. (author)
- Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
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- Strandin, Tomas (author)
- Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
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- Herbert, Andrew S. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA
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- Forsell, Mattias N. E. (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Walker, Laura M. (author)
- Adimab, LLC, United States
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- Chandran, Kartik (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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(creator_code:org_t)
- American Association for the Advancement of Science, 2022
- 2022
- English.
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In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Mittler, Eva
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Wec, Anna Z.
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Tynell, Janne
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Guardado-Calvo, ...
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Wigren, Julia
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Polanco, Laura C ...
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show more...
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O'Brien, Cecilia ...
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Slough, Megan M.
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Abelson, Dafna M ...
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Serris, Alexandr ...
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Sakharkar, Mruna ...
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Pehau-Arnaudet, ...
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Bakken, Russell ...
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Geoghegan, James ...
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Jangra, Rohit K.
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Keller, Markus
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Zeitlin, Larry
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Vapalahti, Olli
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Ulrich, Rainer G ...
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Bornholdt, Zacha ...
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Ahlm, Clas, 1956 ...
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Rey, Felix A.
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Dye, John M.
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Bradfute, Steven ...
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Strandin, Tomas
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Herbert, Andrew ...
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Forsell, Mattias ...
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Walker, Laura M.
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Chandran, Kartik
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Umeå University