Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo.

Autor:	Hansen L; Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway., 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 92037, USA., Zhu X; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Turner JS; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Stadlbauer D; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Vahokoski J; Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway., Schmitz AJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Rizk AA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Alsoussi WB; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Yu W; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Choreño-Parra JA; Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico., Jiménez-Alvarez L; Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Cruz-Lagunas A; Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Zúñiga J; Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico., Mudd PA; Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA., Cox RJ; Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: andrew@scripps.edu., Ellebedy AH; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: ellebedy@wustl.edu., 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. Electronic address: florian.krammer@mssm.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2023 Aug 08; Vol. 56 (8), pp. 1927-1938.e8. Date of Electronic Publication: 2023 Jul 27.
DOI:	10.1016/j.immuni.2023.07.004
Abstrakt:	Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines. Competing Interests: Declaration of interests The Icahn School of Medicine at Mount Sinai has filed patent applications on influenza virus vaccines, including for recombinant neuraminidase vaccines, that name F.K. as inventor. In addition, F.K. is currently consulting for Pfizer, Third Rock Ventures, GSK, and Avimex and has received support for vaccine research and development from Pfizer, GSK, and Dynavax. The Ellebedy laboratory received funding under sponsored research agreements from Moderna, Emergent BioSolutions, and AbbVie that are unrelated to the data presented in the current study. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting. J.S.T., A.J.S., W.B.A., and A.H.E. are recipients of a licensing agreement with Abbvie that is unrelated to the data presented in the current study. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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