Influenza, also called the flu, is an important infectious disease caused by influenza A and B viruses. Vaccines are available that can prevent or reduce influenza symptoms. However, these vaccines provide limited protection primarily due to mismatch between the vaccine components and circulating virus. Interestingly, it has been shown that experimental vaccines based on NA can provide protection in animal models of influenza. Further, natural infection in humans induces antibodies directed against NA which correlate with clinical protection against the flu. Yet, NA is not considered as an essential part of the influenza vaccines that are on the market. One important hurdle that needs to be overcome to include NA as a standardized vaccine component is to have an expression system for intact stable NA. This is challenging since tetrameric NA easily falls apart, thereby losing its activity and its capacity to induce immune protection. Our goal is to set up a robust expression system to produce stable soluble NA as an additional influenza vaccine component. This will be done by combining software-based predictions, information about the structure of NA and a screening method that allows to select stable NA protein out of a mutant library. The stable influenza NAs will be expressed in cell systems that are already in use for production of biologicals in the pharma industry. Finally, we will assess the protective potential of the stabilized NA in experimental models of influenza.