#Influenza #Infection in #Humans Induces Broadly Cross-Reactive and Protective #Neuraminidase-Reactive #Antibodies (Cell, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

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.

Chen YQ1, Wohlbold TJ2, Zheng NY1, Huang M1, Huang Y1, Neu KE3, Lee J4, Wan H5, Rojas KT1, Kirkpatrick E2, Henry C1, Palm AE1, Stamper CT3, Lan LY3, Topham DJ6, Treanor J7, Wrammert J8, Ahmed R8, Eichelberger MC5, Georgiou G4, Krammer F9, Wilson PC10.

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

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]

Keywords: Seasonal Influenza; Avian Influenza; Immunology; Animal models.

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Published by

Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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