(209d) Engineering Self-Assembled Protein Influenza Vaccines for Older and Immunosuppressed Populations

Influenza can infect 9 to 41 million people in the United States each year. Those at higher risk for severe illness include older and immunosuppressed people. Vaccination is an established method to protect against influenza. The Centers for Disease Control recommends (soluble) recombinant influenza vaccines for immunosuppressed and older people compared to a live attenuated vaccine. Also, it is established that protein-based vaccines delivered as nanoparticles can induce higher antibody titers than their soluble counterparts. The multi-valent display of antigens on a particle surface is a significant factor in providing adequate protection. Self-assembled protein nanocages (SAPN) are comprised of coiled-coil motifs and display antigens on both the outer and inner surface of the nanocage. The coiled-coils selected to form cages include leucine-rich zippers homotrimer GCN4 and a heterodimer pair ZR and ZE. GCN4 trimer and ZE/ZR dimer are connected via covalent bonds between cysteine residues on each chain. Without adjuvants, these nanocages induced higher antibody titers and T-cell responses against antigens, portions of the influezna pathogen, presented on the protein nanocage compared to soluble antigens. However, adjuvants can help boost immune responses in older and immunosuppressed populations. We have modified SAPNs to incorporate the protein adjuvant flagellin into the vaccine nanocage by fusion to ZR and will present how this addition affects the biomaterial and antibody and T cell responses compared to soluble adjuvant mixed with SAPN. Overall, SAPNs are a modular vaccine platform that can simultaneously present both antigens and adjuvant when needed for more vulnerable populations.