Most FDA-approved adjuvants for infectious agents boost humoral but not cellular 
immunity, and have poorly-understood mechanisms. Stimulator of interferon genes 
(STING, also known as MITA, MPYS, or ERIS) is an exciting adjuvant target due to 
its role in cyclic dinucleotide (CDN)-driven anti-viral immunity; however, a 
major hindrance is STING's cytosolic localization which requires intracellular 
delivery of its agonists. As a result, STING agonists administered in a soluble 
form have elicited suboptimal immune responses. Delivery of STING agonists via 
particle platforms has proven a more successful strategy, but the opportunity 
for improved formulations and bioactivity remains. In this study we evaluated 
the adjuvant activity of the potent STING agonist, CDN 3'3'-cGAMP (cGAMP), 
encapsulated in acid-sensitive acetalated dextran (Ace-DEX) polymeric 
microparticles (MPs) which passively target antigen-presenting cells for 
intracellular release. This formulation was superior to all particle delivery 
systems evaluated and maintained its bioactivity following a sterilizing dose of 
gamma irradiation. Compared to soluble cGAMP, the Ace-DEX cGAMP MPs enhanced 
type-I interferon responses nearly 1000-fold in vitro and 50-fold in vivo, 
caused up to a 104-fold boost in antibody titers, increased Th1-associated 
responses, and expanded germinal center B cells and memory T cells. Furthermore, 
the encapsulated cGAMP elicited no observable toxicity in animals and achieved 
protective immunity against a lethal influenza challenge seven months 
post-immunization when using CDN adjuvant doses up to 100-fold lower than 
previous reports. For these reasons, Ace-DEX MP-encapsulated cGAMP represents a 
potent vaccine adjuvant of humoral and cellular immunity.