(65c) Broadly Protective Influenza Vaccines Based On the Conserved Hemagglutinin Stalk Region

The emergence of pandemic H1N1 subtype influenza in 2009 emphasizes the need for rapid methods to manufacture large quantities of highly potent influenza vaccines, which would broadly protect against multiple influenza virus strains.  

All commercial influenza vaccines are produced by propagating the virus in embryonated chicken eggs. This technology is slow and requires one embryonated egg per vaccine dose. Cell-free protein synthesis (CFPS) system developed recently in the Swartz lab now allow us to produce large amounts of vaccine proteins at short notice during an epidemic pandemic.

We developed highly potent vaccines for seasonal and pandemic influenzas, which were based on a conserved region of the hemagglutinin (HA) protein. Current commercial vaccines are effective against only a narrow range of influenza virus strains. It is the reason why new vaccines must be generated and administered each year. The novel vaccines in this study would broadly protect against multiple influenza strains. Different methods have been tried to express and get correctly folded trimeric HA stalk domains.

To elicit strong immune responses, we further covalently attached trimeric HA proteins and other immunostimulatory molecules into immune-stimulating virus-like particles (VLPs), using click chemistry. CFPS was used for the production of VLPs with incorporated non-natural amino acids for covalent attachment of other proteins. These VLP constructs containing trimeric HA offer the potential for highly efficacious and broadly protective influenza vaccines.