Quantification of the total neuraminidase content of recent commercially-available influenza vaccines: Introducing a neuraminidase titration reagent.

The protective immunological effects of the influenza neuraminidase (NA) surface protein are of renewed interest but NA content in vaccines remains unstandardized and methods to easily and reliably quantify NA content are unsatisfactory. We describe the use of a recently developed fluorometric titration reagent, TR1, to efficiently quantify the total enzymatically active NA content of six commercially-available influenza vaccines, including split/subunit, inactivated/live and standard /high dose products distributed from 2015/16 to 2017/18 in North America. Considerable differences in active NA content were measured between influenza vaccine products for the same season, with relative content differences between brands generally maintained across seasons. These results highlight the simplicity of use of this reagent, and its unique ability to quantitate enzymatically active NA without the need for specific activities of individual enzymes. The reagent could also prove valuable in assessing the importance of using fully active enzyme to generate protective immune responses.