Technical Abstract: Microparticle adjuvants based on biodegradable polyanhydrides were used to provide controlled delivery of a model antigen, ovalbumin (Ova), to mice. Ova was encapsulated into two different polyanhydride microparticle formulations to evaluate the influence of polymer chemistry on the nature and magnitude of the humoral immune response following administration of a suboptimal dose. Subcutaneous administration of a single dose of polyanhydride microparticles containing 25 µg of Ova elicited humoral immune responses that were comparable in magnitude to that induced by soluble doses of 400 to 1600 µg Ova, demonstrating at least a 16-fold dose-sparing capability. In contrast, the avidity of the Ovaspecific antibodies was greater in mice administered the microparticle formulations in comparison to the soluble doses. The increased avidity was maintained throughout the 12 weektime period. Finally, the microparticle delivery system primed an anamnestic immune response as evidenced by the significant increases in Ova-specific antibody when mice were administered an antigenic challenge of 25 µg of Ova at 12 weeks post-vaccination. Together, these results indicate that encapsulation of antigens into polyanhydride microparticles facilitates isotype switching, establishes immunologic memory and provides a dosage sparing benefit as characterized by a higher quality antibody response.