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

• Type of Material: Article
• Authors: Florian Krammer, Center for Research on Influenza Pathogenesis (CRIP); Ron A.M. Fouchier, Center for Research on Influenza Pathogenesis (CRIP); Maryna C. Eichelberger, Food and Drug Administration; Richard J. Webby, Centers of Excellence for Influenza Research and Surveillance (CEIRS); Kathryn Shaw-Saliba, Centers of Excellence for Influenza Research and Surveillance (CEIRS); Hongquan Wan, Food and Drug Administration; Patrick C. Wilson, Centers of Excellence for Influenza Research and Surveillance (CEIRS); Richard Compans, Emory University; Ioanna Skountzou, Emory University; Arnold S. Monto, Centers of Excellence for Influenza Research and Surveillance (CEIRS)
• Language: English
• Date: 2018-04-03
• Publisher: American Society for Microbiology: Open Access Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Krammer et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/mBio.02332-17
• Title of Journal or Parent Work: mBio
• ISSN: 2150-7511
• Volume: 9
• Issue: 2
• Start Page: e02332-17
• End Page: e02332-17
• Grant/Funding Information: NA-focused work in our laboratories is supported by the following: NIAID CEIRS contracts HHSN272201400008C (F.K., R.A.M.F.), HHSN272201400007C (K.S.-S.), HHSN272201400006C (R.J.W.), HHSN272201400005C (P.C.W.), and HHSN272201400004C (I.S., R.W.C.); NIAID grants R01 AI117287 (focused on influenza B NA, F.K.), U19 AI109946 (P.C.W.), and R56 AI097150 (A.S.M.); Biomedical Advanced Research and Development Authority (BARDA) contract HHSO100201500033C (R.A.M.F.); and CBER (FDA) intramural funds (H.W., M.C.E.).
• Keywords: VIRAL NEURAMINIDASE; Microbiology; INFECTED DENDRITIC CELLS; universal influenza virus vaccine; PANDEMIC H1N1; Life Sciences & Biomedicine; MONOCLONAL-ANTIBODIES; HEMAGGLUTININ STALK; A VIRUS; A(H3N2) VIRUSES; HUMAN AIRWAY EPITHELIUM; Science & Technology; influenza vaccines; neuraminidase; LINKED LECTIN ASSAY; INTRAVIRIONIC ANTIGENIC-COMPETITION
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Microbiology

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.