“…While these early studies point to the potential of CDNs as adjuvants promoting both T cell and humoral responses to subunit vaccines, the potency of STING agonists as parenteral adjuvants for systemic immunity remains unclear. For example, while vaccines administered with modest doses of cdGMP (5 μg) have been reported to elicit substantial antibody titers in response to highly immunogenic model antigens, such as ovalbumin (OVA) or β-galactosidase (15,17,18), this same Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation.…”