Development of a universal group 2 influenza virus vaccine using chimeric hemagglutinin constructs

The stalk domain of the hemagglutinin (HA) has become the prime target for universal influenza virus vaccine development in the last few years. Unlike the HA head domain, the immunosubdominant stalk domain is conserved to a higher level within each influenza virus HA group. Sequential vaccination with chimeric HA (cHA) vaccine constructs consisting of the same HA stalk and exotic head domains has proven to re-direct the immune response towards the stalk domain. This vaccination concept provides the basis for the development of more broadly cross-protective vaccines that are less affected by antigenic drift and shift, one of the main drawbacks of currently marketed influenza vaccines. Most influenza virus vaccines are licensed as inactivated split vaccines. They are manufactured based on HA content with little to no information and standardization of neuraminidase (NA) content. Virus inactivation is generally performed with alkylating agents such as formalin (FA) or β-propiolactone (βPL), rendering the virus unable to infect or replicate. Though safe, whole inactivated virus vaccines can be highly reactogenic. Virus splitting with detergents like sodium deoxycholate (SDCO) and Triton X-100 (TX-100), which dissociate the virus into smaller parts while maintaining a good immunogenicity profile, are typically employed. To date, there are several studies assessing the effect of a variety of inactivating and splitting agents on influenza viruses, but little is known about the impact of combining these agents on HA stalk conformation and NA activity. Please click Download on the upper right corner to see the full abstract