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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 ...

  • American Association for the Advancement of Science (AAAS),2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-211153
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-211153URI
  • https://doi.org/10.1126/scitranslmed.adg1855DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Serris, AlexandraCNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France (author)
  • Esterman, Emma S.Adimab LLC, Lebanon, NH,USA (author)
  • Florez, CatalinaU.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States; The Geneva Foundation, Tacoma, WA, USA (author)
  • Polanco, Laura C.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • 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)
  • Slough, Megan M.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Tynell, JanneUmeå universitet,Institutionen för klinisk mikrobiologi,Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland(Swepub:umu)jaty0002 (author)
  • Gröning, RemigiusUmeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)regr0024 (author)
  • Sun, YanDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Abelson, Dafna M.Mapp Biopharmaceutical Inc., San Diego, CA, USA (author)
  • Wec, Anna Z.Adimab LLC, Lebanon, NH, USA (author)
  • Haslwanter, DeniseDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Keller, MarkusInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany (author)
  • Ye, ChunyanCenter for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States (author)
  • Bakken, Russel R.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States (author)
  • Jangra, Rohit K.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Dye, John M.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States (author)
  • Ahlm, Clas,1956-Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)clah0001 (author)
  • Rappazzo, C. GarrettAdimab LLC, Lebanon, NH, USA (author)
  • 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)
  • Zeitlin, LarryMapp Biopharmaceutical Inc., San Diego, CA, USA (author)
  • Geoghegan, James C.Adimab LLC, Lebanon, NH, USA (author)
  • Bradfute, Steven B.Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States (author)
  • Sidoli, SimoneDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Forsell, Mattias N. E.Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)mafo0173 (author)
  • Strandin, TomasZoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland (author)
  • Rey, Felix A.CNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France (author)
  • Herbert, Andrew S.U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States (author)
  • Walker, Laura M.Adimab LLC, Lebanon, NH, USA (author)
  • Chandran, KartikDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA (author)
  • Guardado-Calvo, PabloCNRS UMR3569, Structural Virology Unit, Institut Pasteur, Paris, France (author)
  • 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)

Related titles

  • In:Science Translational Medicine: American Association for the Advancement of Science (AAAS)15:7001946-62341946-6242

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