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MBio. 2018 Apr 3;9(2). pii: e02332-17. doi: 10.1128/mBio.02332-17.

NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines?

Krammer F1,2,3, Fouchier RAM4,3,5, Eichelberger MC6, Webby RJ3,7,8, Shaw-Saliba K3,9,10,11, Wan H6, Wilson PC3,12,13, Compans RW3,14,15,16, Skountzou I3,14,15,16, Monto AS3,12,17.

Author information

1
Center for Research on Influenza Pathogenesis (CRIP), New York, New York, USA florian.krammer@mssm.edu.
2
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3
Centers of Excellence for Influenza Research and Surveillance (CEIRS)‡.
4
Center for Research on Influenza Pathogenesis (CRIP), New York, New York, USA.
5
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
6
Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
7
St. Jude Center of Excellence for Influenza Research and Surveillance, Memphis, Tennessee, USA.
8
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
9
Johns Hopkins Center of Excellence for Influenza Research and Surveillance, Baltimore, Maryland, USA.
10
Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
11
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
12
New York Influenza Center of Excellence (NYICE), New York, New York, USA.
13
Department of Medicine, the Knapp Center for Lupus and Immunology Research, Section of Rheumatology, the University of Chicago, Chicago, Illinois, USA.
14
Emory-UGA Center of Excellence for Influenza Research and Surveillance, Atlanta, Georgia, USA.
15
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
16
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
17
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Abstract

Neuraminidase is one of the two surface glycoproteins of influenza A and B viruses. It has enzymatic activity that cleaves terminal sialic acid from glycans, and that activity is essential at several points in the virus life cycle. While neuraminidase is a major target for influenza antivirals, it is largely ignored in vaccine development. Current inactivated influenza virus vaccines might contain neuraminidase, but the antigen quantity and quality are varied and not standardized. While there are data that show a protective role of anti-neuraminidase immunity, many questions remain unanswered. These questions, among others, concern the targeted epitopes or antigenic sites, the potential for antigenic drift, and, connected to that, the breadth of protection, differences in induction of immune responses by vaccination versus infection, mechanisms of protection, the role of mucosal antineuraminidase antibodies, stability, and the immunogenicity of neuraminidase in vaccine formulations. Reagents for analysis of neuraminidase-based immunity are scarce, and assays are not widely used for clinical studies evaluating vaccines. However, efforts to better understand neuraminidase-based immunity have been made recently. A neuraminidase focus group, NAction!, was formed at a Centers of Excellence for Influenza Research and Surveillance meeting at the National Institutes of Health in Bethesda, MD, to promote research that helps to understand neuraminidase-based immunity and how it can contribute to the design of better and broadly protective influenza virus vaccines. Here, we review open questions and knowledge gaps that have been identified by this group and discuss how the gaps can be addressed, with the ultimate goal of designing better influenza virus vaccines.

KEYWORDS:

influenza vaccines; neuraminidase; universal influenza virus vaccine

PMID:
29615508
PMCID:
PMC5885027
DOI:
10.1128/mBio.02332-17
[Indexed for MEDLINE]
Free PMC Article

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