Instead of exhorting their teenagers that they'll be sorry about that tattoo 10 years (or two months) down the road, parents might one day be dragging their toddlers to get tattooed. With DNA.

"DNA vaccines are very simple to make, are relatively cheap, are extremely stable and, most importantly, are safe to use," John Haanen, head of the immunotherapy group at The Netherlands Cancer Institute in Amsterdam, told BioWorld Today via email.

However, "results in humans have been disappointing in terms of induction of sizable immune responses [enough to protect against viral disease, for instance.]" For that reason, though DNA vaccines are under development for diseases including HIV and malaria, the immune response to DNA vaccines often has been both relatively slow and weak. Therefore, protein vaccines still are the predominant form of vaccination, though Haanen pointed out that they are "more difficult to make, are less stable, and may differ in efficacy between batches."

Research that Haanen and his colleagues, from The Netherlands Cancer Institute and the Johns Hopkins University in Baltimore, published online in Nature Medicine might change that. Their secret weapon: a tattoo gun.

The classic way to administer vaccines is intramuscular injection. But Haanen pointed out that "muscle is not a very good tissue for raising an immune response because it lacks all the ingredients, such as dendritic cells and other cells of the innate immune system. Skin has a natural barrier function and is densely populated with different kinds of immune cells such Langerhans cells in the epidermis and dermal DC in the dermis.

"By injecting the DNA over a large surface area, we figured we might get a better induction of an immune response," Haanen said. "Adriaan Bins, a graduate student in my lab, came up with the idea of using a tattoo device."

The researchers first used that tattoo gun to deliver a DNA plasmid encoding an epitope against influenza A, and showed that they could induce a T-cell response by delivering the vaccine in that manner. Comparing muscle and skin delivery of the same vaccine, the scientists found that muscle injection led to much greater antigen production - 10 times greater than with tattooing. The antigen also was expressed for much longer; while antigen production after muscle injection peaked after a week and was detectable for a month, tattooing led to peak antigen production after six hours that lasted for only four days.

So far, those results seem to favor muscle injections; but when the researchers next tested the abilities of both methods to induce T-cell responses, a very different picture emerged. In the words of Haanen and his colleagues, "although antigen production is markedly greater upon intramuscular delivery, presentation of this antigen to na ve T cells is markedly more efficient upon intradermal DNA delivery."

While only "marginal" T-cell responses were induced by muscle injection, tattooing led to a much more robust T-cell response despite the lower levels of antigen. Vaccine delivery via tattooing also led to an antibody response to influenza A.

The researchers tested different time intervals for repeated DNA delivery and found that by vaccinating repeatedly with an interval of a few days, they could induce both T-cell and antibody responses relatively rapidly. When mice were exposed to influenza A virus 14 days after DNA vaccination, those that had been tattooed fared significantly better than their muscle-injected peers.

They also used their method to induce an immune response to tumors, and were successful there, as well. When mice first were injected with tumor cells and vaccinated a few days later, tattooed mice had much smaller tumors after two weeks than injected mice; their survival time also was about triple that of mice receiving either the injected DNA vaccine or a control tattoo vaccine.

The researchers particularly noted that their findings made the use of DNA vaccines more likely in situations in which a speedy immune response is of the essence, such as influenza, Ebola and severe acute respiratory syndrome, though Haanen didn't rule out the possibility of ultimately using the approach for routine childhood vaccinations, assuming its promise holds up. The researchers currently are performing a proof-of-principle study in a large animal model; Haanen said that preliminary results look very promising, though he also pointed out that "we have to await the final results." If those final results continue to look good, "we have planned an early phase clinical trial in melanoma patients for the beginning of next year."