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Structural and mech...
Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
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- Mittler, Eva (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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- Serris, Alexandra (author)
- CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
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- Esterman, Emma S. (author)
- Adimab LLC, Lebanon, NH,USA
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- Florez, Catalina (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States; The Geneva Foundation, Tacoma, WA, USA
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- Polanco, Laura C. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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- O'Brien, Cecilia M. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States; The Geneva Foundation, Tacoma, WA, USA
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- Slough, Megan M. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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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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- Gröning, Remigius (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Sun, Yan (author)
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
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- Abelson, Dafna M. (author)
- Mapp Biopharmaceutical Inc., San Diego, CA, USA
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- Wec, Anna Z. (author)
- Adimab LLC, Lebanon, NH, USA
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- Haslwanter, Denise (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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- Keller, Markus (author)
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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- Ye, Chunyan (author)
- Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
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- Bakken, Russel R. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
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- Jangra, Rohit K. (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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- Dye, John M. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
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- Ahlm, Clas, 1956- (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Rappazzo, C. Garrett (author)
- Adimab LLC, Lebanon, NH, USA
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- Ulrich, Rainer G. (author)
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany; Partner site: Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), Greifswald-Insel Riems, Germany
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- Zeitlin, Larry (author)
- Mapp Biopharmaceutical Inc., San Diego, CA, USA
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- Geoghegan, James C. (author)
- Adimab LLC, Lebanon, NH, USA
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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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- Sidoli, Simone (author)
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
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- Forsell, Mattias N. E. (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Strandin, Tomas (author)
- Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
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- Rey, Felix A. (author)
- CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
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- Herbert, Andrew S. (author)
- U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
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- Walker, Laura M. (author)
- Adimab LLC, Lebanon, NH, USA
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- Chandran, Kartik (author)
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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- Guardado-Calvo, Pablo (author)
- CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2023
- 2023
- English.
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
- 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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- Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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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- By the author/editor
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Mittler, Eva
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Serris, Alexandr ...
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Esterman, Emma S ...
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Florez, Catalina
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Polanco, Laura C ...
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O'Brien, Cecilia ...
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show more...
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Slough, Megan M.
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Tynell, Janne
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Gröning, Remigiu ...
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Sun, Yan
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Abelson, Dafna M ...
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Wec, Anna Z.
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Haslwanter, Deni ...
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Keller, Markus
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Ye, Chunyan
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Bakken, Russel R ...
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Jangra, Rohit K.
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Dye, John M.
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Ahlm, Clas, 1956 ...
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Rappazzo, C. Gar ...
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Ulrich, Rainer G ...
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Zeitlin, Larry
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Geoghegan, James ...
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Bradfute, Steven ...
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Sidoli, Simone
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Forsell, Mattias ...
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Strandin, Tomas
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Rey, Felix A.
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Herbert, Andrew ...
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Walker, Laura M.
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Chandran, Kartik
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Guardado-Calvo, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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Umeå University