Nanomedicinal delivery of stimulator of interferon genes agonists: recent advances in virus vaccination

The discovery of stimulator of interferon genes (STING) and their agonists as primary components that link antiviral innate and adaptive immunity has motivated growing research on STING agonist-mediated immunotherapy and vaccine development. To overcome the delivery challenge in shuttling highly polar STING agonists, typically in the form of cyclic dinucleotides, to target cells and to STING proteins in cellular cytosol, numerous nanoformulation strategies have been implemented for effective STING activation. While many STING-activating nanoparticles are developed to enhance anticancer immunotherapy, their adoption as vaccine adjuvant has vastly propelled antiviral vaccination efforts against challenging public health threats, including HIV, influenza and coronaviruses. In light of the COVID-19 pandemic that has thrusted vaccine development into the public spotlight, this review highlights advances in nanomedicinal STING agonist delivery with an emphasis on their applications in antiviral vaccination. The stimulator of interferon genes (STING) is a protein inside cells that plays a critical role in the body's immune response against viruses. Infection by a virus activates STING proteins, triggering defense mechanisms for virus eradication. Many strategies involving nanoparticles, particles with nanometric size, have been developed to activate STING proteins for therapeutic purposes. Vaccine candidates based on STING-activating nanoparticles have shown highly promising results against challenging public health threats, including HIV, influenza and coronaviruses. In this review article, the development of STING-activating nanoparticles and their capability in improving vaccination efforts in the recent literature are highlighted.