The DNA vaccine has proven to be one of the most promising applications in the field of gene therapy. Due to its unique ability to readily induce humoral as well as cellular immune responses, it attracted great interest when the concept was first confirmed in the early 1990s. After thousands of articles related to the DNA vaccine were published, scientists began to realize that although the DNA vaccine is very effective in small animal models, its effectiveness in recent clinical trails is rather disappointing. Therefore, current effort has been shifted to understanding the different performance of the DNA vaccine in mouse and large animal models and on how to transfer the success of the DNA vaccine in small animals to large animals and humans.