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Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody

Mittler, Eva (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Serris, Alexandra (author)
CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
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
Polanco, Laura C. (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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
Slough, Megan M. (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Tynell, Janne (author)
Umeå universitet,Institutionen för klinisk mikrobiologi,Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
Gröning, Remigius (author)
Umeå universitet,Institutionen för klinisk mikrobiologi
Sun, Yan (author)
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
Abelson, Dafna M. (author)
Mapp Biopharmaceutical Inc., San Diego, CA, USA
Wec, Anna Z. (author)
Adimab LLC, Lebanon, NH, USA
Haslwanter, Denise (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Keller, Markus (author)
Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
Ye, Chunyan (author)
Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
Bakken, Russel R. (author)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
Jangra, Rohit K. (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Dye, John M. (author)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
Ahlm, Clas, 1956- (author)
Umeå universitet,Institutionen för klinisk mikrobiologi
Rappazzo, C. Garrett (author)
Adimab LLC, Lebanon, NH, USA
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
Zeitlin, Larry (author)
Mapp Biopharmaceutical Inc., San Diego, CA, USA
Geoghegan, James C. (author)
Adimab LLC, Lebanon, NH, USA
Bradfute, Steven B. (author)
Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
Sidoli, Simone (author)
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
Forsell, Mattias N. E. (author)
Umeå universitet,Institutionen för klinisk mikrobiologi
Strandin, Tomas (author)
Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
Rey, Felix A. (author)
CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
Herbert, Andrew S. (author)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
Walker, Laura M. (author)
Adimab LLC, Lebanon, NH, USA
Chandran, Kartik (author)
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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.
In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
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)

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