The use of cytokines and chemokines as genetic adjuvants for plasmid DNA vaccines

The direct injection of a naked plasmid DNA vaccine encoding a foreign antigen results in plasmid uptake and protein expression leading to the induction of antigen-specific cellular and humoral immune responses. The ability of DNA vaccine-elicited immune responses to protect against viral and bacterial infections, parasites, cancers, and autoimmune diseases has been well documented in numerous animal models. Phase I human clinical trials have shown that experimental DNA vaccines are safe and well tolerated, however, these preliminary studies indicate that measures must be taken to improve vaccine immunogenicity. One approach to improve the immunogenicity of DNA vaccines is through the co-delivery of cytokine expression plasmids as genetic adjuvants. Studies in a variety of animal models clearly demonstrate that plasmid DNA-encoded immunomodulatory cytokines not only alter the magnitude and direction of the DNA vaccine-elicited immune response, but can also improve vaccine efficacy. These studies suggest that the use of immunomodulatory cytokines with plasmid DNA vaccines may allow clinicians to tailor the resulting immune response to more closely resemble the correlates of protection for a given pathogen.