Polymer patches could replace needles and enable more effective DNA vaccines
By David Szondy
January 29, 2013
Taking a two-month-old in for vaccination shots and watching them get stuck with six needles in rapid succession can be painful for child and parent alike. If the work of an MIT team of researchers pans out, those needles may be thing of the past thanks to a new dissolvable polymer film that allows the vaccination needle to be replaced with a patch. This development will not only make vaccinations less harrowing, but also allow for developing and delivering vaccines for diseases too dangerous for conventional techniques.
Vaccines don’t prevent people from getting diseases – at least, not on their own. They work by causing the body’s immune system to kick into action before a real threat of infection exists. When the body encounters an infection, such as a virus, it generates antibodies that are specific to that infection. If a person encounters the same infection again, the body tags the incoming microbes with the antibodies, which act like beacons that mark the microbes for destruction by the body’s immune defenses. Unfortunately, that means that the only way to gain immunity to a disease is to catch it.
A vaccine is a sort of artificial disease that tells the body what the genuine virus is like without, ideally, the peril of actual infection. When a vaccine is injected, the body creates antibodies that are specific to the virus, so if the person encounters it, the immune system is primed and ready.
There are two basic kinds of vaccines. The first uses attenuated viruses. This common and relatively simple method uses “dead” or inactive viruses. As far as the body is concerned, it’s the proteins that encase the virus that are important, not whether or not the virus is “alive.” So long as the immune system can get a taste of those proteins, the rest doesn't matter.
Unfortunately, even with attenuated viruses there’s still a remote chance of an infection, so one alternative is to make the vaccine from the proteins in the virus. These proteins may be from the virus itself or produced synthetically. This method is more difficult and time consuming and may not be appropriate for viruses that mutate frequently or come in wide varieties.
The problem of making vaccines for some viruses is a very difficult affair because they are too dangerous to risk even in an attenuated form. HIV is one example of this and, ironically, the first vaccine, the famous smallpox vaccine, was created for just this reason. Inoculating people with the smallpox virus often resulted in them contracting the full-blown disease, so Edward Jenner’s discovery that a vaccine made from relatively mild cowpox was a major breakthrough.
What Jenner didn’t know was that the reason his vaccine worked was because the proteins in cowpox are similar enough to those in smallpox to induce an immune reaction that produces antibodies that react to both diseases.
A new approach developed by MIT researchers takes the vaccine a step further back in the life process. Instead of using viruses or proteins it uses the DNA strands that produce the proteins. This has had some success in rodents in research over the past two decades, but human tests haven’t been effective.
The problem is getting the DNA into the body. It can’t just be injected because the body destroys it before the immune system has a chance to respond. The MIT approach involves delivering the DNA through the skin using a dermal patch made of multiple layers of polymer film. When applied as a patch, these film layers are embedded under the skin using microneedles.
When the film comes into contact with water in the body tissues, it dissolves and carries the embedded DNA with it. As the polymer is absorbed by the body cells, it protects the DNA. By altering the number of layers and their affinity to water, the speed of the DNA absorption can be controlled so that the DNA is released slowly to give the body time to respond. This way, the body can build a proper immunity without any danger of infection.
According to the team, the polymer vaccine has other advantages. Since there are no proper needles and the microneedles are too short to reach the pain nerves, it doesn't hurt.
“You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin,” said Darrell Irvine, an MIT professor of biological engineering and materials science and engineering.
It’s also more stable than conventional vaccines, so it can be shipped and stored at room temperature, is biodegradable, can target skin immune cells for greater efficacy, and particular diseases can be targeted.
“If you're making a protein vaccine, every protein has its little quirks, and there are manufacturing issues that have to be solved to scale it up to humans. If you had a DNA platform, the DNA is going to behave the same no matter what antigen it’s encoding,” said Irvine.
The polymer can also be used to introduce antigens and other small molecules into the body and as a vaccine delivery system it contains an adjuvant, which consists of strands of RNA molecules that cause inflammation and draws immune cells into the area to speed up the reaction.
Tests of the vaccination polymer on rats have been positive and the team has also carried out primate tests using simian HIV DNA on macaque skin samples, which showed DNA transportation where injection would have been ineffective. Further primate tests are planned with human tests to follow.
The results were published in the January 27 issue of Nature Materials.
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