(680b) Biomaterial-Mediated Enhancement of Vaccination through Co-Delivery of DNA and Small Molecule Adjuvants

Over the last several decades, biomaterials have become important in a multitude of biological contexts from basic biomedical research, to diagnostics, to new medical treatments and therapies. Drug delivery in particular has benefitted substantially from biomaterials that have provided increasing control over the kinetics, concentrations, and specificity with which small molecule, nucleic acid, and protein cargo are delivered. In this talk, we will describe a novel particle-based DNA vaccination platform built around i) biodegradable, FDA-approved materials and ii) the encapsulation and co-delivery of immunomodulatory small molecule adjuvants. Microparticles or nanoparticles with a polymer core consisting of poly(lactide-co-glycolide) or novel bioresorbable polymers enveloped by a conformal phospholipid bilayer shell were synthesized by an emulsion/solvent evaporation process. Inclusion of charged or reactive lipids enabled reversible association of DNA plasmids with the surfaces of these materials, facilitating DNA delivery and the prolonged expression of DNA-encoded antigens in vivo. To enhance the function of these particles in vaccination, we encapsulated small-molecule immunomodulators in the polymeric core to allow amplification or tuning of the quality of immune responses generated following vaccination. The potential of many small molecule immunomodulatory agents has been hindered by poor solubility and short half-lives in vivo, thus, the approach described here is designed to permit continuous dosing via sustained drug release from particles co-loaded with drugs and antigen-encoding DNA. Using optimized particle synthesis protocols and formulations, the ability of these materials to mediate immune responses in vivo following immunization with model antigens and HIV-relevant antigens will also be described. Because biomaterials allow the engineering of specific properties and co-delivery of multiple agents, this approach could serve as a means for enhancing existing DNA vaccination strategies for HIV, as well as for the broader vaccine field.