Neuraminidase, the Forgotten Surface Antigen, Emerges as an Influenza Vaccine Target for Broadened Protection

For 50 years it has been known that antibodies to neuraminidase (NA) protect against infection during seasonal and pandemic influenza outbreaks. However, NA is largely ignored in the formulation and standardization of our current influenza vaccines. There are a number of factors that contributed to this antigen being forgotten, including the lack of an easily performed test to measure NA antibody. With the availability of that test, it has been possible to show its independent contribution to protection in various situations. The challenge now is to make it possible to include known amounts of NA in investigational vaccines or to routinely measure NA content in licensed vaccines. Vaccines containing optimal amounts of NA may be particularly useful when there are antigenic changes, either drift or shift, in the hemagglutinin because NA immunity offers broad protection. It is now time to remember the NA as we work toward improved influenza vaccines.