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Structural and mech...
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Mittler, EvaDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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American Association for the Advancement of Science (AAAS),2023
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-211153
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-211153URI
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https://doi.org/10.1126/scitranslmed.adg1855DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Serris, AlexandraCNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
(author)
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Esterman, Emma S.Adimab LLC, Lebanon, NH,USA
(author)
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Florez, CatalinaU.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States; The Geneva Foundation, Tacoma, WA, USA
(author)
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Polanco, Laura C.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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O'Brien, Cecilia M.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States; The Geneva Foundation, Tacoma, WA, USA
(author)
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Slough, Megan M.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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Tynell, JanneUmeå universitet,Institutionen för klinisk mikrobiologi,Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland(Swepub:umu)jaty0002
(author)
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Gröning, RemigiusUmeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)regr0024
(author)
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Sun, YanDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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Abelson, Dafna M.Mapp Biopharmaceutical Inc., San Diego, CA, USA
(author)
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Wec, Anna Z.Adimab LLC, Lebanon, NH, USA
(author)
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Haslwanter, DeniseDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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Keller, MarkusInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
(author)
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Ye, ChunyanCenter for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
(author)
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Bakken, Russel R.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
(author)
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Jangra, Rohit K.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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Dye, John M.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
(author)
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Ahlm, Clas,1956-Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)clah0001
(author)
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Rappazzo, C. GarrettAdimab LLC, Lebanon, NH, USA
(author)
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Ulrich, Rainer G.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
(author)
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Zeitlin, LarryMapp Biopharmaceutical Inc., San Diego, CA, USA
(author)
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Geoghegan, James C.Adimab LLC, Lebanon, NH, USA
(author)
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Bradfute, Steven B.Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States
(author)
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Sidoli, SimoneDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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Forsell, Mattias N. E.Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)mafo0173
(author)
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Strandin, TomasZoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland
(author)
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Rey, Felix A.CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
(author)
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Herbert, Andrew S.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States
(author)
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Walker, Laura M.Adimab LLC, Lebanon, NH, USA
(author)
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Chandran, KartikDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
(author)
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Guardado-Calvo, PabloCNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
(author)
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Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USACNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France
(creator_code:org_t)
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In:Science Translational Medicine: American Association for the Advancement of Science (AAAS)15:7001946-62341946-6242
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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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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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