Improving polymer-mediated DNA vaccine delivery.

Abstract

Vaccination using antigen-encoding plasmid DNA has great potential to generate strong immune response against delivered antigen. In order to effectively generate immune response, antigen must be delivered to antigen presenting cells, primarily dendritic cells (DCs). Using cationic polymers as a delivery vehicle can provide many advantages, including protection of DNA from degradation, ability to add targeting moieties, and easy modification of structure to optimize various properties. We have investigated the use of polyplexes as a DNA delivery vehicle in a variety of settings. We demonstrated the feasibility of using the CD40L as a DC targeting moiety, a protein capable of both binding and stimulating DC maturation, using coated nanoparticles. We have also studied the possibility of delivering antigen through transfection of bystander cells rather than direct expression by DCs using an in vitro model. We confirmed the ability of these DCs to present antigen, become mature, and stimulate T cells. Finally, we studied the interaction of cationic polymer complexes in vivo, both in respect to local tissue dispersion and interaction with specific cell types, using fluorescently labeled DNA. Through these experiments we have illuminated potential pathways for optimizing DNA vaccine efficiency using polymer complexes with slightly different structures.