Agonist Based Adjuvants

Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs), C-type lectin receptors (CLRs), cyclic AMP-GMP synthase and stimulator of interferon genes (the cGAS-STING pathway), and AIM2-like receptors (ALRs) are all involved in pathways targeted by agonist-based adjuvants. TLRs are innate immune receptors that are directly or indirectly responsible for detecting pathogen-associated molecular patterns (PAMPs) and responding by activating innate and adaptive immune pathways. Naturally occurring and synthetic TLR agonists can exploit these endogenous immune signaling pathways to enhance and modulate vaccine responses, making them excellent vaccine adjuvants. Each TLR has specific tissue localization and downstream gene signaling pathways, and TLR agonists can be combined with other TLRs or alternative adjuvants to create combination adjuvants with synergistic or regulatory effects. STING agonists are widely used in various research fields. In addition to inducing natural immune responses, they are involved in other DNA or RNA sensor signaling pathways, autophagy, endoplasmic reticulum stress, and apoptosis. Beyond their anti-tumor and immunogenic properties, STING agonists have also emerged as a new class of immunotherapy drugs and vaccine adjuvants.