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Cell. 2018 Apr 5;173(2):417-429.e10. doi: 10.1016/j.cell.2018.03.030.

Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.

Author information

1
Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
3
The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
4
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731, USA.
5
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
6
Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
7
Division of Infectious Disease, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
8
Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
9
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@mssm.edu.
10
Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. Electronic address: wilsonp@uchicago.edu.

Abstract

Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.

KEYWORDS:

B cell; human immunology; humoral immune response; influenza; monoclonal antibody; neuraminidase; therapeutics; vaccine; virus infection

PMID:
29625056
PMCID:
PMC5890936
[Available on 2019-04-05]
DOI:
10.1016/j.cell.2018.03.030
[Indexed for MEDLINE]

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