STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant

The current pandemic highlights the need for effective vaccines against respiratory viruses. An ideal vaccine should induce robust and long-lasting responses with high manufacturing scalability. We use an adjuvant comprised of a Stimulator of Interferon Genes (STING) agonist incorporated in a scalable microparticle platform to achieve durable protection against the influenza virus. This formulation overcomes the challenges presented by the cytosolic localization of STING and the hydrophilicity of its agonists. We evaluated a monoaxial formulation of polymeric acetalated dextran microparticles (MPs) to deliver the STING agonist cyclic GMP-AMP (cGAMP) which achieved > 10x dose-sparing effects compared to other published work. Efficacy was evaluated in ferrets, a larger animal model of choice for influenza vaccines. cGAMP MPs with recombinant hemagglutinin reduced viral shedding and improved vaccine outcomes compared to a seasonal influenza vaccine. Importantly, sustained protection against a lethal influenza infection was detected a year after a single dose of the vaccine-adjuvant.

Automated summary

The current pandemic emphasizes the importance of effective vaccines against respiratory viruses. This study presents a vaccine strategy using a scalable microparticle platform containing a STING agonist as an adjuvant, which provides durable protection against the influenza virus. Animal studies demonstrate that this vaccine-adjuvant combination can reduce viral shedding, improve vaccine outcomes, and provide sustained protection even a year after a single dose.