Approaches to enhance the efficacy of DNA vaccines.

DNA vaccines consist of antigen-encoding bacterial plasmids that are capable of inducing antigen-specific immune responses upon inoculation into a host. This method of immunization is advantageous in terms of simplicity, adaptability, and cost of vaccine production. However, the entry of DNA vaccines and expression of antigen are subjected to physical and biochemical barriers imposed by the host. In small animals such as mice, the host-imposed impediments have not prevented DNA vaccines from inducing long-lasting, protective humoral, and cellular immune responses. In contrast, these barriers appear to be more difficult to overcome in large animals and humans. The focus of this article is to summarize the limitations of DNA vaccines and to provide a comprehensive review on the different strategies developed to enhance the efficacy of DNA vaccines. Several of these strategies, such as altering codon bias of the encoded gene, changing the cellular localization of the expressed antigen, and optimizing delivery and formulation of the plasmid, have led to improvements in DNA vaccine efficacy in large animals. However, solutions for increasing the amount of plasmid that eventually enters the nucleus and is available for transcription of the transgene still need to be found. The overall conclusions from these studies suggest that, provided these critical improvements are made, DNA vaccines may find important clinical and practical applications in the field of vaccination.