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DNA Vaccines - Dna Vaccination Techniques

genetic clinical plasmid cells immune immunization

DNA vaccination involves immunization with a circular piece of DNA, known as a plasmid, that contains the gene (or genes) that code for an antigen. When injected into an individual, the plasmid is taken up by cells and its genetic information is translated into the immunizing protein. This enables the host immune system to respond to the antigen as it is presented to other cells.

In many respects, this process is reminiscent of what occurs during a viral infection, when viral proteins are expressed within host cells. Thus, a DNA vaccine is somewhat like a very simple, nonreplicating virus. However, plasmid DNA vaccines do not replicate within the host, and therefore do not infect neighboring cells, as occurs during a viral infection.

This innovation in vaccination strategy was discovered some years ago, but the active development of this technology only began after Stephen Johnston's group at the University of Texas Southwestern Medical Center demonstrated that plasmid DNA can induce the formation of antibodies against an encoded protein in 1992. Johnston's group was able to show that when mice are innoculated with plasmid DNA encoding human growth hormone, the mice produce antibodies against the hormone.

Shortly thereafter, another research group reported that a protective cell-mediated immune response against influenza virus followed immunization with plasmid DNA encoding an influenza virus protein. This study demonstrated that DNA-based immunization stimulates both components of the immune system and helped to establish that DNA immunization is capable of inducing a protective response against infection.

There are two basic ways to inoculate with plasmid-based vaccines. The first involves direct inoculation into muscle tissue, with the plasmid DNA suspended in a saline (salt) solution ("naked" DNA). The DNA is eventually taken up into nearby cells and processed to express the encoded antigen. The other method uses a high-pressure device, a so-called gene gun, to propel DNA-coated gold particles into cells in the skin. This method is sometimes referred to as biolistic particle inoculation. Both methods are widely used, and newer methods for the delivery of plasmid DNA vaccines are currently in development.

As of December 2001 there are several clinical studies in progress to evaluate the effectiveness of DNA vaccination. Most of these studies were targeted against viral infectious agents, such as HIV, hepatitis B, and influenza virus. However, there are also studies in progress to develop DNA vaccines against malaria and tuberculosis. There are even several efforts to develop DNA vaccines against various forms of cancer, an approach which seems to offer significant hope for the future.

Darrell R. Galloway

Bibliography

Tang, D. C., M. Devit, and S. A. Johnston. "Genetic Immunization Is a Simple Method for Eliciting an Immune Response." Nature 356 (1992): 152-154.

Ulmer, Jeffrey B., John J. Donnelly, and Margaret A. Liu. "DNA Vaccines Promising: A New Approach to Inducing Protective Immunity." ASM News 62 (1996): 476-479.

Weiner, David B., and Ronald C. Kennedy. "Genetic Vaccines." Scientific American 281 (1999): 50-57.

Wolff, J. A., et al. "Direct Gene Transfer into Mouse Muscle in vivo." Science 247 (1990): 1465-1468.

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