Microparticles and DNA Vaccines

Developing deoxyribonucleic acid (DNA) vaccines potent enough to be clinically useful will likely require an understanding of the mechanism of action both of naked DNA vaccines themselves, and of adjuvant formulations that may be combined with DNA. Mechanisms of action attributed to naked DNA vaccines described thus far include transfection of keratinocytes (1), muscle cells (2), and dendritic cells (DCs) (3), and activation of innate immunity by pathogen- associated molecular patterns (PAMPs) such as unmethylated CpG-containing immunostimulatory sequences (4). Improving the immunogenicity of DNA vaccines has focused on four areas of investigation: increasing stability and efficiency of transfection, maximizing the ability of the antigen to be presented by DCs, and stimulating the immune response to the target antigen. A collective body of work demonstrating the versatility and mechanism of action of microparticle/DNA vaccine formulations supports promise of developing effective DNA vaccines utilizing this potent adjuvant/delivery system. Understanding the mechanism of action of DNA/microparticles provides both a basis for rational optimization of the formulation and basic insights into efficient induction of immunity.