Strategies towards improved influenza vaccines

Influenza viruses cause seasonal epidemics and, periodically, unpredictable pandemics, both leading to substantial morbidity and mortality worldwide. Vaccination represents the cornerstone of influenza protection. Clearly, the benefits from annual influenza vaccination among specific target groups, including the elderly, in terms of prevention of laboratory-confirmed influenza and complications or death due to influenza are substantial. Nonetheless, there is considerable room for improvement. For example, there are still limitations to the current influenza vaccine production technology. Furthermore, the sudden appearance of a pandemic influenza virus subtype, such as the H1N1pdm09 virus in 2009, in combination with the inflexible production process, makes an appropriate rapid response to a pandemic outbreak of influenza problematic. Fortunately, there are positive developments in this regard, which relate to production of both seasonal as well as pandemic influenza vaccines. In addition, recently, a number of advances have been made in the development of improved and more broadly protective influenza vaccines. The studies described in this thesis were designed to contribute to the further improvement of current inactivated influenza vaccines and to explore avenues for the development of innovative, more broadly protective, influenza vaccines. In pursuit of these aims, we followed a number of different approaches