Researchers use a modified off-the-shelf tattoo gun to increase the effectiveness of DNA vaccines in mice. Photo courtesy Martin Müller The best defense against fast-moving diseases like bird flu may one day be a DNA vaccine tattoo under your skin.

Researchers are experimenting with slightly modified tattoo guns to deliver DNA vaccines – a potent form of vaccine that is easily engineered in vast quantities to protect against diseases like flu, HIV and malaria.

DNA vaccines are not new, but scientists have struggled to devise an effective way to get them into the body. The tattoo gun, which implants the DNA vaccine as "ink" under the surface of the skin, could prove the ideal delivery mechanism, making DNA vaccines viable for the first time.

"Tattooing could lead to more commercial uses of DNA vaccines," said Martin Müller, a researcher at the German Cancer Research Center in Heidelberg, who devised the method.

DNA vaccines have long promised "programmable" vaccines that can be quickly genetically engineered to mimic any emerging virus and grown quickly inside bacteria. But unlike the disarmed viruses used in standard vaccines, DNA injected into the body doesn't naturally give rise to immunity.

But Müller claims his technique does the trick, getting an immune system response comparable to regular vaccines.

"We get about 200-fold higher responses compared to conventional injection (of a DNA vaccine)," he said.

Using a modified tattoo gun, Müller tattooed mice with DNA programmed to create human papillomavirus proteins, which generated high levels of antibodies and white blood cells tuned to those antigens.

But the technique comes at a cost – pain – that could limit its application. And there's no easy way around it because the injury associated with tattooing, Mülller said, is likely a key ingredient in generating an effective immune response.

The trauma is probably required, he said, because the disturbance to the skin naturally draws extra immune system cells to the area. The increased number of cells encountering the viral proteins provokes a more potent immune system response.

Standard vaccines are made of disarmed versions of viruses that are often grown inside chicken eggs. DNA vaccines are a simpler version, made of just the virus' genes placed into a circular DNA structure called a plasmid, then grown in bacteria. The technique makes producing commercial quantities of DNA vaccines much faster than current vaccine technologies.

"It's possible to make huge quantities of plasmid DNA," said Bob Belshe, director of the Center for Vaccine Development at Saint Louis University.

Once injected into the patient's body, the plasmids enter cells and begin to produce proteins, which generate an immune response. The immune response is more complete with DNA vaccines than with standard vaccines because they also stimulate the production of killer T cells, which are important in controlling some types of infection, Belshe said.

However, Belshe pointed out that vaccine-making can take several decades. "It's an exciting technology with a ways to go," he said.

DNA vaccines have rekindled interest in developing new vaccines, which traditionally have not been lucrative. In late 2006, Pfizer bought DNA vaccine company PowerMed for its needleless injection techniques.

With interest in DNA vaccines growing, the German group is not alone in looking into tattooing as a means of vaccine delivery. A Danish team led by Adriaan Bins also published a paper on the technique in Nature Medicine.

Müller's team used an off-the-shelf tattoo gun (sans colored ink) for their work, which is published online in the open-access journal, Genetic Vaccines and Therapy.

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