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Science. 2019 Oct 25;366(6464):499-504. doi: 10.1126/science.aay0678.

Broadly protective human antibodies that target the active site of influenza virus neuraminidase.

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
2
Department of Biotechnology, University of Natural Resources and Life Sciences, A-1190 Vienna, Austria.
3
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Pediatrics, Columbia Irving Medical Center, New York, NY 10032, USA.
6
NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY 10032, USA.
7
Division of Emergency Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. wilson@scripps.edu ellebedy@wustl.edu florian.krammer@mssm.edu.
9
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
10
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson@scripps.edu ellebedy@wustl.edu florian.krammer@mssm.edu.
11
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. wilson@scripps.edu ellebedy@wustl.edu florian.krammer@mssm.edu.

Abstract

Better vaccines against influenza virus are urgently needed to provide broader protection against diverse strains, subtypes, and types. Such efforts are assisted by the identification of novel broadly neutralizing epitopes targeted by protective antibodies. Influenza vaccine development has largely focused on the hemagglutinin, but the other major surface antigen, the neuraminidase, has reemerged as a potential target for universal vaccines. We describe three human monoclonal antibodies isolated from an H3N2-infected donor that bind with exceptional breadth to multiple different influenza A and B virus neuraminidases. These antibodies neutralize the virus, mediate effector functions, are broadly protective in vivo, and inhibit neuraminidase activity by directly binding to the active site. Structural and functional characterization of these antibodies will inform the development of neuraminidase-based universal vaccines against influenza virus.

PMID:
31649200
DOI:
10.1126/science.aay0678

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