The Emerging Role of DNA Vaccines

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Vaccines composed of DNA are injected into subjects whose own cellular machinery translates the nucleotide sequences into peptides. The peptides are presented in the context of MHC class I molecules, and are therefore capable of inducing a brisk cellular immune response, in contrast with traditional vaccines which produce mainly a humoral immune response. DNA may be transferred into the cell by retrovirus, vaccinia virus or adenovirus vectors or by attachment to cationically charged molecules such as liposomes, calcium salts or dendrimers.
Alternatively, the desired gene may be directly inserted into a plasmid and the naked DNA simply injected intramuscularly. Naked plasmid DNA vaccines bypass the problem of safety and manufacturing issues arising when viral vectors are used, and also avoid complications or interference from an immune response directed at the delivery vector. For all delivery methods, there is the unproved potential for insertional mutagenesis. There is also the concern of inducing tolerance rather than resistance or anti-DNA antibody formation, leading to autoimmune diseases.
There are no DNA vaccines on the market, nor even any published data showing efficacy in humans. Human trials are underway testing the safety and efficacy of DNA vaccines against influenza, malaria, hepatitis B virus, HIV, herpes simplex virus, colon cancer and cutaneous T cell lymphoma. While these early studies have only just begun to provide suggestions of vaccine efficacy, the concepts brought forth by DNA vaccines have dramatically changed the way many investigators in the basic sciences are approaching their work.