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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses

Mittler, Eva (författare)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Wec, Anna Z. (författare)
Adimab, LLC, United States
Tynell, Janne (författare)
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 (författare)
Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
Wigren, Julia (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Polanco, Laura C. (författare)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
O'Brien, Cecilia M. (författare)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA
Slough, Megan M. (författare)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Abelson, Dafna M. (författare)
Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
Serris, Alexandra (författare)
Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
Sakharkar, Mrunal (författare)
Adimab, LLC, United States
Pehau-Arnaudet, Gerard (författare)
Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
Bakken, Russell R. (författare)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States
Geoghegan, James C. (författare)
Adimab, LLC, United States
Jangra, Rohit K. (författare)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Keller, Markus (författare)
Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
Zeitlin, Larry (författare)
Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
Vapalahti, Olli (författare)
Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland; Veterinary Biosciences, Veterinary Faculty, University of Helsinki, Helsinki, Finland
Ulrich, Rainer G. (författare)
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
Bornholdt, Zachary A. (författare)
Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA
Ahlm, Clas, 1956- (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Rey, Felix A. (författare)
Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France
Dye, John M. (författare)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States
Bradfute, Steven B. (författare)
Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
Strandin, Tomas (författare)
Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
Herbert, Andrew S. (författare)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA
Forsell, Mattias N. E. (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Walker, Laura M. (författare)
Adimab, LLC, United States
Chandran, Kartik (författare)
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
Engelska.
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

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)

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