Novel delivery strategies for DNA

DNA vaccination has been dubbed the third revolution in vaccine development by some observers ever since its promising in vivo application in the early 1990s. The method is an attractive vaccine avenue because of its inherent simplicity as well as its relative cost effectiveness. DNA vaccination is also appealing because it is possible to produce large quantities of vaccine in a short period of time. In comparison with other conventional vaccines, DNA vaccines are stable and have a long shelf life. The most intriguing property of a DNA vaccine is that it can promote long-lasting humoral and cellular immunity leading to protective and/or therapeutic effects in preclinical and clinical tests. However, the immunogenicity of a DNA vaccine is hindered by suboptimal delivery of the DNA to cells, especially in large animals. Several other concerns have been raised in the field including the potential for DNA integration into the host genome and the possibility of autoimmune responses due to the long-term presence of the foreign DNA. In this review, we discuss different approaches to optimize DNA vaccines in order to improve their immunogenicity and delivery. Discussion will include the choice of the antigen, codon optimization to increase antigen expression, choice of optimal expression vectors and proper adjuvants; there will be a special focus on several novel delivery methods. We will also discuss the potential strategies to address the concerns in DNA vaccine application.