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Author Notes:

florian.krammer@mssm.edu (F.K.); wilsonp@uchicago.edu (P.C.W.).

Complete list of author contributions available in full text.

We especially thank all study participants.

We thank Jenna Guthmiller for critical comments.

We thank Daniel Kaplan and Paul Bunduc for technical assistance.

We thank St. Jude Children’s Research Hospital for providing plasmids that were used to generate the reassortant viruses.

The authors declare no competing interests.

Subjects:

Research Funding:

This project was funded in parts from the National Institute of Allergy and Infectious Disease; National Institutes of Health grant numbers U19AI082724 (PCW), U19AI109946 (PCW), U19AI057266 (PCW), U19AI109946 (FK); and the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS, HHSN272201400005C, PCW, DJT and JT, and HHSN272201400008C, FK); a CEIRS training grant to (TJW); and by the FDA (JW and MCE).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • VIRUS SURFACE GLYCOPROTEINS
  • HUMAN MONOCLONAL-ANTIBODIES
  • VIRAL NEURAMINIDASE
  • UNITED-STATES
  • PANDEMIC H1N1
  • IN-VIVO
  • B-CELLS
  • HEMAGGLUTININ
  • ANTIGEN
  • EPITOPES

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

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Journal Title:

Analytical Cellular Pathology / Cellular Oncology

Volume:

Volume 173, Number 2

Publisher:

, Pages 417-+

Type of Work:

Article | Post-print: After Peer Review

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. Current influenza vaccines predominantly produce antibodies targeting the viral hemagglutinin (HA). However, during natural infection, the body also produces antibodies targeting the viral neuraminidase (NA). These NA antibodies can provide robust and broad protection and could potentially be elicited prophylactically or via new vaccine strategies or used therapeutically.

Copyright information:

© 2018 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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