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Patching up vaccine issues
CAMBRIDGE, Mass.—Vaccines have long been a staple of the medical industry, and have gained new popularity in recent years as a prophylactic for diseases such as cancer and against evolving diseases such as the flu. Despite their usefulness, however, there are often difficulties in how to develop the vaccines without exposing patients to undue risk, especially since the most common form of a vaccine consists of inactive versions of viruses.
But now recent work has shown that DNA—which was first proven to induce strong immune response in rodents injected with DNA coding for viral proteins—might be a possible alternative for a vaccine basis.
A team of researchers from the Massachusetts Institute of Technology (MIT) has developed a type of vaccine-delivery film that could provide increased effectiveness when it comes to DNA vaccines. The approach consists of a patch made up of several layers of polymers that contain the DNA vaccine. The polymer films are then implanted underneath the skin by way of microneedles, which puncture the skin just deep enough to deliver the DNA to immune cells in the epidermis, but not deeply enough for the nerve endings in the dermis to register pain. Once they've been implanted, the films slowly degrade once in contact with water, thereby releasing the vaccine over the span of several days or weeks, and as that happens, the DNA strands get tangled with pieces 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," Darrell Irvine, an MIT professor of biological engineering and materials science and engineering and a senior author of the study, said in a press release.
Should this approach prove successful in humans and make it to commercialization, it could be a huge boon for vaccinations in terms of ease of shipment and administration, a lack of biohazardous waste such as syringes and increased stability thanks to the fact that they don't include viruses.
The amount of DNA and rate of delivery can be controlled by adjusting 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 and allowing them to encounter the vaccine DNA and begin to engender an immune response.
The researchers tested the polymer films in mouse models, with strong results, and also tested it on primates. The team applied a polymer film embedded with DNA that codes for proteins of the simian version of HIV to lab-cultured skin samples from a macaque—a species of monkey that is very similar 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 samples treated with the polymer film, the researchers were able to easily detect the DNA, which Irvine noted is hopefully "an indication that this will translate to large animals and hopefully humans."
The tests showed the MIT team that their approach engendered an immune response as good as or better than that seen with electroporation, a method that involves injecting DNA under the skin, then using electrodes to generate an electric field, thereby opening small pores in the cell membranes in the skin that the DNA can pass through. This process has noticeable drawbacks, however, given that it can be painful, effectiveness varies and the application of electricity can cause lasting damage to the cells.
"It's showing some promise but it's certainly not ideal, and it'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 in non-human primates before tests in humans are considered, and should it prove effective, these patches could be used to vaccinate people against a range of different diseases since the embedded DNA sequence can be switched easily to target various diseases.
Irvine and Paula Hammond, the David H. Koch Professor in Engineering, are the senior authors of the paper, with Peter DeMuth, a graduate student in biological engineering, as the lead author. The paper, "Polymer multilayer tattooing for enhanced DNA vaccination," appeared in the Jan. 27 online issue of Nature Materials.