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.