DNA Vaccines

A DNA vaccine uses foreign DNA to express an encoded protein and stimulate the body's immune system. It represents a new way to immunize against infectious disease that is potentially less expensive than classic vaccination forms.

Classic Vaccines

One of the greatest achievements in the history of medicine has been the development of vaccination. The use of vaccines has saved more lives than all other medical procedures combined, and represents one of the highest points in civilization's technical accomplishments. Vaccines are used to mobilize the immune system to prevent or combat infectious disease caused by exposure to viruses, bacteria, or parasites.

A vaccine works by mimicking an infectious agent and inducing a protective immune response in the host, without actually causing the disease. Successful vaccination provides protection for individuals by making them immune to the disease, and it protects whole populations by hindering the spread of the infectious agent.

Historically, vaccines have consisted of formulations using live, noninfectious (attenuated) microbes that resemble the original pathogen ; whole organisms that have been killed; or purified by-products of the infectious agent. More recently, some vaccines have used recombinant DNA technology to genetically engineer purified proteins from infectious agents.

All of these classic vaccines are based on the principle of using a protein to stimulate the immune system. In other words, the individual is immunized with a protein vaccine consisting of either a modified pathogen or some protein or proteins derived from that pathogen. When the immune system encounters a foreign protein (called an antigen ), it mounts a two-pronged defense. It produces proteins called antibodies, which can bind and neutralize the antigen, and it produces specific immune cells, which work to eliminate those host cells that have been infected by the microbe. Thus our immune system is capable of producing two distinct types of responses to combat infectious microbes: An antibody response and a cell-mediated response. Typically, vaccines activate only the antibody response to an infectious microbe.

Advantages of DNA Vaccines

DNA vaccines represent a new approach to immunization, in that an individual is directly inoculated (injected) with DNA that genetically encodes one or more of the antigens associated with the infectious agent. In effect, the recipient of a DNA vaccine produces the immunizing protein (antigen) within his own cells as a result of the immunization process.

This revolutionary approach to vaccination offers many advantages over conventional vaccines. A major advantage is that DNA vaccination stimulates both the antibody and cell-mediated components of the immune system, whereas conventional protein vaccines usually stimulate only the antibody response. Furthermore, DNA vaccines are simpler to produce and store than conventional vaccines, and are therefore less expensive. Preliminary studies to date indicate that DNA vaccines appear to be very safe and to produce no side effects.

DNA Vaccination Techniques

DNA vaccination involves immunization with a circular piece of DNA, known as a plasmid, that contains the gene (or genes) that code for anantigen . 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.

see also Immune System Genetics; Plasmid.

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.