Cobra Hemagglutinin and cGAMP Loaded Ace-Dex Microparticles Provide a Broadly Active and Shelf-Stable Influenza Vaccine Platform

Current FDA-approved influenza vaccines are limited by variable year to year efficacy, low immunogenicity, and poor stability outside of cold-chain storage. Polymeric microparticles can overcome many of these issues to provide an improved influenza vaccine platform. Here, an acetalated dextran microparticle platform is used to encapsulate a broadly active influenza COBRA immunogen and the adjuvant cGAMP. Microparticles are fabricated via the highly scalable electrospray method. Mice vaccinated with acetalated dextran microparticles loaded with COBRA and cGAMP produced antibodies with the ability to neutralize antigenically distinct influenza viruses. The microparticles also induced a potent cellular response against the COBRA immunogen. Finally, after storage for 3 months at 40 degrees C or 6 months at 24 degrees C, the microparticles produced as strong of an immune response as microparticles stored at -20 degrees C for the same amount of time. Overall, acetalated dextran microparticles provide a promising platform for a broadly active influenza vaccine. Current influenza vaccines are limited by cold-chain storage requirements and poor year to year efficacy. To address these limitations, a broadly active influenza antigen and a STING agonist are encapsulated in acetalated dextran microparticles. These microparticles induce a broadly neutralizing antibody response, a strong cellular response, and stability when stored outside the cold-chain. image