Influenza Vaccines Utilizing Hemagglutinin Constructs with Covalent Attachment to Virus-Like Particles

Influenza vaccines are important for both seasonal outbreaks as well as pandemic threats. A common antigen for vaccines is the hemagglutinin (HA) protein located on the surface of the virus. We have produced several constructs of HA using E. coli based cell-free protein synthesis (CFPS). CFPS is also a useful method for the production of immune-stimulating virus-like particles (VLPs) with incorporated non-natural amino acids for covalent attachment of other proteins. We have shown the feasibility of covalent attachment of HA to VLPs, along with other immunostimulatory molecules such as GMCSF and CpG DNA, using click chemistry. These VLP constructs containing HA offer the potential for highly efficacious and broadly protective influenza vaccines.