Purpose: Allergen-specific immunotherapy (SIT) requires dozens of subcutaneous injections over 3 to 5years in order to control IgE-mediated hypersensitivity, which is a T-helper 2 (Th2)-associated pathology. This study investigates the use of poly(lactide-co-glycolide) (PLGA) microparticles combined with immunostimulatory oligodeoxynucleotide (CpG), as well as protamine in SIT. Materials and Methods: We prepared microparticle formulations with the major allergen of bee venom, phospholipase A2 (PLA2), and analyzed the effect of co-encapsulated or admixed CpG in both naïve and bee venom allergic mice. Results: Mice immunized with microparticles containing only PLA2 induced weak antibody responses. In contrast, the combination with CpG resulted in strong PLA2-specific antibody responses. The presence of CpG was required for the induction of the Th1-associated isotype IgG2a, and the titers of IgG2a in sensitized mice correlated with a better protection against an allergen challenge. The effect of CpG was further strengthened when protamine was co-encapsulated for complexation of CpG. Conclusions: This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duratio
