(194x) Combination Nanoadjuvants for Influenza Vaccines

Each year influenza A virus (IAV) causes significant morbidity and mortality, leading to approximately 200,000 hospitalizations and 36,000 deaths annually in the United States. In addition, the emergence of pandemic strains highlights a critical need for vaccine preparedness plans. While vaccines against IAV exist, they have been plagued by antigen mismatch issues, resulting in poor efficacy. Thus, new vaccine technologies are needed to provide robust, durable protection against influenza. Polyanhydride nanoparticles have been shown to be a dual-functional platform technology that is capable of both delivering and adjuvanting subunit proteins. While polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) against influenza are promising, recent literature suggests that a combination of adjuvants may enhance vaccine responses by targeting different immune mechanisms. In this work, polyanhydride nanoparticles encapsulating H1N1 hemagglutinin (HA) and nucleoprotein (NP) were co-formulated with novel pentablock copolymer micelles. These micelles have been shown to promote the rapid development of antibody responses. In this work, we demonstrate that the combination vaccine enhanced antibody responses compared to either adjuvant alone. Additionally, the combination vaccine was found to be protective against a live virus challenge in a single dose with reduced viral loads in the lungs and may be optimized for alternative routes of delivery. Altogether, these data demonstrate the combination nanovaccine to be a promising platform technology for efficacious influenza vaccines.