Acetalated : a spoonful of sugar helps the medicine (and ) go down

Kristy Ainslie, PhD Associate Professor Division of Pharmacoengineering and Molecular Pharmaceutics UNC Eshelman School of Pharmacy

Polymeric microparticles (MPs) and adjuvants can be used to enhance protein or subunit vaccines because protein based are often poorly immunogenic. By controlling and adjuvant release MPs can also be used to understand cell activation kinetics and the significant impact antigen and adjuvant release has on innate and adaptive immune responses. Through understanding how antigen and adjuvant release is controlled with MPs, we can have precise temporal control over the peak and duration of protective immunity and improve safety profiles. In order to study the effect of tunable adjuvant or antigen delivery on the generation of adaptive immunity, we have used acetalated dextran (Ace-DEX) MPs. Ace- DEX is an acid-sensitive biopolymer that when formulated into MPs can be used for passive targeting of antigen presenting cells and once phagocytosed, it has triggered release in the low pH environment of the phagosome. Also, Ace-DEX has tunable degradation that can be controlled based on polymer relative cyclic coverage (CAC). We have used Ace-DEX MPs of varying degradation profiles to deliver several antigens and adjuvants. We have observed that different adjuvant and antigens peak at unique CACs (degradation rates). Also, peak antibody and cellular responses are observed and significantly different when adjuvant and antigen are in separate MPs of unique CAC. Moreover, this difference translates into protection against a lethal infectious challenge, in a mouse model. Overall, we display that we can fine-tune subunit vaccine responses using our Ace-DEX MP formulation, as well as begin to understand immune response kinetics.

Biography Dr. Kristy M. Ainslie is an Associate Professor with appointments in the Division of Pharmacoengineering and Molecular Pharmaceutics, within the Eshelman School of Pharmacy, UNC Department of Microbiology and Immunology, and the UNC/NC State Department of Biomedical Engineering. Her research focuses on the use of biomaterials and immunology to develop new immune-modulatory therapies that treat and prevent infectious diseases, autoimmune diseases, and cancer. As a postdoctoral scholar at the University of California, San Francisco, she researched the microfabrication of oral drug delivery vehicles and the immune response of nanobiomaterials. Prior to that, she completed a Ph.D. and M.S. in Chemical Engineering at The Pennsylvania State University and her B.S. in Chemical Engineering at Michigan State University.