| Autor: |
Matthew D. Gallovic, Robert D. Junkins, Adam M. Sandor, Erik S. Pena, Christopher J. Sample, Ariel K. Mason, Leslee C. Arwood, Rebecca A. Sahm, Eric M. Bachelder, Kristy M. Ainslie, Gregory D. Sempowski, Jenny P.-Y. Ting |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
J Control Release |
| ISSN: |
0168-3659 |
| Popis: |
The COVID-19 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 used an adjuvant comprised of a Stimulator of Interferon Genes (STING) agonist incorporated in a microparticle (MP) platform that can be produced in a scalable manner to achieve durable protection against influenza virus challenge. 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 MPs to deliver the STING agonist cyclic GMP-AMP (cGAMP) in the context of innate immune activation and subunit vaccination against influenza hemagglutinin. In mice, acetalated dextran cGAMP MPs potently activated antigen presenting cells in vitro and lead to protective humoral and early T cell immune responses with >10X dose-sparing effects compared to other published work. Efficacy was also evaluated in ferrets, the larger animal model of choice for influenza vaccine testing. cGAMP MPs with recombinant hemagglutinin reduced viral shedding and improved vaccine outcomes compared to a seasonal influenza vaccine formulation. Importantly, sustained protection against influenza infection was detected a year after a single dose of the vaccine with cGAMP MPs adjuvant. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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