What is DNA Vaccines?
DNA vaccines are circular pieces of DNA, known as plasmids, that contain the sequence(s) for one or more protein antigens and replicate autonomously from the cell chromosome.. When the DNA plasmid is introduced into human cells, the human cells express the protein encoded on the plasmid, subsequently stimulating an immune response against the encoded antigen.
A DNA vaccine consists of a small circular DNA plasmid encoding one or more protein antigens under the control of a mammalian promoter. The mammalian promoter drives expression of the vaccine antigens in cells that take up the DNA. By controlling the location of the expressed protein, DNA vaccines can be used to produce a variety of types of immunity, including antibody, T helper cell (CD4+ T cell), and cytotoxic T lymphocyte (CTL, CD8+ T cell) mediated immunity.1
A major challenge for recombinant protein and inactivated vaccines is that they primarily stimulate a humoral immune response. For many pathogens, especially intracellular pathogens, this is not a sufficient immune response to prevent disease. CTLs are important immune cells for fighting intracellular infections. Because DNA vaccines cause expression of the antigen in the cytosol of the host cell, antigen protein peptides are presented to the immune system in MHC class I molecules. Recognition of foreign peptide in the MCH I molecule stimulates the CD8+ T cell response. There is some ability to tune the immune response through the use of adjuvants; however, humoral antibody response is generally weak with DNA vaccines.
Although DNA vaccines can be adjusted to produce a variety of types of immune response, thus far they have failed to produce a strong enough immune response to provide protection on their own. Moving forward, DNA vaccines are primarily being evaluated as priming vaccines that provide initial exposure of the individual to an antigen. This priming step is then followed by vaccination using an alternative vaccine, such as a recombinant protein or viral vectored vaccine, as a booster. This strategy is called a heterologous prime-boost approach and aims to provide a stronger overall immune response.
- Liu MA (2003) “DNA vaccines: a review.” Journal of Internal Medicine 253: 402-410.
- CDC press release, CDC and Fort Dodge Animal Health Achieve First Licensed DNA Vaccine, available here.
Although there are no DNA vaccines currently in use in humans, DNA vaccines are in development for a variety of neglected tropical diseases. The overall strengths and weaknesses of DNA vaccines for viral, bacterial, and parasitic diseases are summarized here.
|Potential to elicit a wide range of immune responses (both humoral and cellular)||Regulatory pathway uncertain as no DNA vaccines are approved for humans|
|Potential for combination with other vaccination technologies, especially as part of prime-boost regimens||Humoral immune responses likely lower than with recombinant protein or inactivated vaccines|
|For large multicellular helminths that are difficult to culture, live attenuated and inactivated vaccines are impractical; DNA vaccines offer a potential alternative||For many neglected diseases, vaccines of other technology types are in more advanced stages of development. Clear competitive advantage must be demonstrated in clinical trials.|
|Purification and proper folding of proteins not required||
DNA vaccines benefit from the widespread use and understanding of plasmid DNA for a variety of biological manipulations such as generating gene knockouts and episomal expression of genes. For more detailed information on the design of DNA vaccines, see the recent review by Williams et al., available here.