The bacterial second messenger cyclic diGMP exhibits potent adjuvant properties

Current concepts of severe asthma

“…Type I IFNs are also induced in defense against virus infections. c-di-GMP can function as an adjuvant for the induction of Th1 and Th17 immune responses mixed with a low Th2 immune response (95). Given these attributes of c-di-GMP, we recently used a combination of the allergen HDM and c-di-GMP to induce a mixed Th1 and Th17 immune response along with a low Th2 response in the airways of mice that were detectable even in the presence of a high dose of CS, mimicking the CS-refractory immune response in severe asthmatics (48).…”

Selection of Adjuvants for Enhanced Vaccine Potency

“…Its application as a systemic or mucosal vaccine adjuvant has been recently reviewed [406]. Subcutaneous co-administration of β-galactosidase (β-al) and bis-(3',5')-cyclic dimeric guanosine monophosphate (cdiGMP) elicited strong cellular immune responses, characterized by a balanced Th1/Th2 pattern, and significantly higher antigen-specific serum IgG titers than β-al alone in mice [407]. In a different study, it was found that intraperitoneal coadministration of cdiGMP with pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to alum adjuvant [405].…”

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

“…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.…”