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Tytuł:
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Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site.
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Autorzy:
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Stadlbauer D; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
McMahon M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Zhu X; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Wan H; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Carreño JM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
O'Dell G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
Khalil Z; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Luksza M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
van Bakel H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Simon V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ellebedy AH; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. .
Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. .; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA. .
Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. .
Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA. .
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Źródło:
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Nature communications [Nat Commun] 2022 Dec 21; Vol. 13 (1), pp. 7864. Date of Electronic Publication: 2022 Dec 21.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Original Publication: [London] : Nature Pub. Group
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MeSH Terms:
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Antibodies, Monoclonal*/chemistry
Antibodies, Monoclonal*/immunology
Influenza A Virus, H3N2 Subtype*/immunology
Influenza A Virus, H3N2 Subtype*/metabolism
Neuraminidase*/chemistry
Neuraminidase*/immunology
Humans ; Antibodies, Viral/chemistry ; Antibodies, Viral/metabolism ; Catalytic Domain/immunology ; Catalytic Domain/physiology ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza A virus ; Influenza, Human/immunology ; Influenza, Human/metabolism
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Grant Information:
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75N93019C00051 United States AI NIAID NIH HHS; 75N93021C00014 United States AI NIAID NIH HHS; HHSN272201400008C United States AI NIAID NIH HHS
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Substance Nomenclature:
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0 (Antibodies, Monoclonal)
0 (Antibodies, Viral)
0 (Hemagglutinin Glycoproteins, Influenza Virus)
EC 3.2.1.18 (Neuraminidase)
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Entry Date(s):
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Date Created: 20221221 Date Completed: 20230125 Latest Revision: 20230708
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Update Code:
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20240104
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PubMed Central ID:
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PMC9772378
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DOI:
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10.1038/s41467-022-35586-7
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PMID:
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36543789
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Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.
(© 2022. The Author(s).)
