CAMBRIDGE, Mass.—Vaccines have long been a staple of themedical industry, and have gained new popularity in recent years as aprophylactic for diseases such as cancer and against evolving diseases such asthe flu. Despite their usefulness, however, there are often difficulties in howto develop the vaccines without exposing patients to undue risk, especiallysince the most common form of a vaccine consists of inactive versions ofviruses.
But now recent work has shown that DNA—which was firstproven to induce strong immune response in rodents injected with DNA coding forviral proteins—might be a possible alternative for a vaccine basis.
A team of researchers from the Massachusetts Institute ofTechnology (MIT) has developed a type of vaccine-delivery film that couldprovide increased effectiveness when it comes to DNA vaccines. The approachconsists of a patch made up of several layers of polymers that contain the DNAvaccine. The polymer films are then implanted underneath the skin by way ofmicroneedles, which puncture the skin just deep enough to deliver the DNA toimmune cells in the epidermis, but not deeply enough for the nerve endings inthe dermis to register pain. Once they've been implanted, the films slowlydegrade once in contact with water, thereby releasing the vaccine over the spanof several days or weeks, and as that happens, the DNA strands get tangled withpieces of the polymer, which protects the DNA and eases its entry into cells.
"You just apply the patch for a few minutes, take it off,and it leaves behind these thin polymer films embedded in the skin," DarrellIrvine, an MIT professor of biological engineering and materials science andengineering and a senior author of the study, said in a press release.
Should this approach prove successful in humans and make itto commercialization, it could be a huge boon for vaccinations in terms of easeof shipment and administration, a lack of biohazardous waste such as syringesand increased stability thanks to the fact that they don't include viruses.
The amount of DNA and rate of delivery can be controlled byadjusting the number of polymer layers and the hydrophobic nature of the film,respectively. The researchers included an adjuvant in the polymer film as well,which, along with the gradual release of the DNA, boosts the immune response.Specifically, the adjuvant is comprised of strands of RNA that mimic viral RNA,which provokes inflammation, triggering immune cells to flock to the area andallowing them to encounter the vaccine DNA and begin to engender an immuneresponse.
The researchers tested the polymer films in mouse models,with strong results, and also tested it on primates. The team applied a polymerfilm embedded with DNA that codes for proteins of the simian version of HIV tolab-cultured skin samples from a macaque—a species of monkey that is verysimilar to humans and thought to share roughly 93 percent of our DNA sequence.DNA that was injected regularly was quickly broken down, but in skin samplestreated with the polymer film, the researchers were able to easily detect theDNA, which Irvine noted is hopefully "an indication that this will translate tolarge animals and hopefully humans."
The tests showed the MIT team that their approach engenderedan immune response as good as or better than that seen with electroporation, amethod that involves injecting DNA under the skin, then using electrodes togenerate an electric field, thereby opening small pores in the cell membranesin the skin that the DNA can pass through. This process has noticeabledrawbacks, however, given that it can be painful, effectiveness varies and theapplication of electricity can cause lasting damage to the cells.
"It's showing some promise but it's certainly not ideal, andit's not something you could imagine in a global prophylactic vaccine setting,especially in resource-poor countries," noted Irvine in a press release.
The next step will be to conduct additional tests innon-human primates before tests in humans are considered, and should it proveeffective, these patches could be used to vaccinate people against a range ofdifferent diseases since the embedded DNA sequence can be switched easily totarget various diseases.
Irvineand Paula Hammond, the David H. Koch Professor in Engineering, are the seniorauthors of the paper, with Peter DeMuth, a graduate student in biologicalengineering, as the lead author. The paper, "Polymer multilayer tattooing forenhanced DNA vaccination," appeared in the Jan. 27 online issue of Nature Materials.
