Adjuvant is an essential component in subunit vaccines. Many agonists of pathogen recognition receptors have been developed as potent adjuvants to optimize the immunogenicity and efficacy of vaccines. Recently discovered cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has attracted much attention as it is a key mediator for modulating immune responses. Vaccines adjuvanted with STING agonists are found to mediate a robust immune defense against infections and cancer. In this review, we first discuss the mechanisms of STING agonists in the context of vaccination. Next, we present recent progress in novel STING agonist discovery and the delivery strategies. We next highlight recent work in optimizing the efficacy while minimizing toxicity of STING agonist-assisted subunit vaccines for protection against infectious diseases or treatment of cancer. Finally, we share our perspectives of current issues and future directions in further developing STING agonists for adjuvanting subunit vaccines.

Advanced Drug Delivery Reviews
Available online 29 October 2021, 114020