3D printed microneedle patches can help bring vaccines to the masses
Getting vaccines to people around the world who need them is often complicated, as many need to be put in cold storage – making it difficult to ship them to remote areas that don’t have the necessary infrastructure.
Researchers from the renowned Massachusetts Institute of Technology have found a solution to this issue. Just as meat, fish and chicken, homes, plastic parts and much more are being produced in a 3D printer, researchers at MIT’s Koch Institute for Integrative Cancer Research have suggested a mobile vaccine printer that could be scaled up to produce hundreds of vaccine doses in a day. The researchers wrote that this type of printer could be used anywhere vaccines were needed. It can fit on a small tabletop.
Most vaccines, including mRNA vaccines, have to be refrigerated while stored, making it difficult to stockpile them or send them to locations where those temperatures can’t be maintained. In addition, they need syringes, a needle, and trained healthcare professionals to administer.
To overcome this obstacle, the MIT group set out to discover a method of producing vaccines at will. The original purpose of the MIT team, before Covid-19 was introduced, was to develop a device which could rapidly produce and distribute vaccines during epidemics like Ebola. A device of this type could be sent to a remote village or refugee camp, or to a military base in order to quickly vaccinate large numbers of people.
“We could someday have on-demand vaccine production,” said Ana Jaklenec, an MIT research scientist. “If, for example, there was an Ebola outbreak in a particular region, one could ship a few of these printers there and vaccinate the people in that location.”
A syringe filled with Pfizer’s COVID-19 vaccine is seen at a community vaccination center that was set up in Valley Stream (New York) (credit: REUTERS).
The printer can produce patches that contain hundreds of microneedles and vaccine. These patches could then be applied to the skin so the vaccine would dissolve without the use of a conventional injection. The vaccine patches, once printed, can be stored at room temperature for several months.
Researchers showed that they could produce thermostable Covid-19 RNA vaccinations using the printer. These vaccines would be stable at a range of temperatures, and induce an immune response in mice that was comparable to that induced by injected RNAs. Senior authors of the study are Jaklenec as well as Prof. Robert Langer from the Koch Institute. The paper’s lead authors are former MIT postdoc Aurelien vander Straeten, former MIT graduate student Morteza Sarmadi and postdoctoral researcher John Daristotle.
The researchers chose to develop a novel vaccine delivery system based upon patches that are about the size and shape of a thumbnail, but contain hundreds of microneedles. These vaccines are currently being developed for a variety of diseases including polio. measles, and rubella. The needle tips dissolve when the patch is placed on the skin. This releases the vaccine.
“When Covid-19 started, concerns about vaccine stability and vaccine access motivated us to try to incorporate RNA vaccines into microneedle patches,” Daristotle said. The “ink” that the researchers used to print the vaccine-containing microneedles includes RNA vaccine molecules that are encapsulated in lipid nanoparticles that help them to remain stable for long periods of time.
What are the requirements for making patches?
Inks also contain polymers which can be easily moulded into the desired shape. They remain stable even at higher temperatures or room temperature for several weeks. Researchers discovered that a 50/50 mixture of polyvinylpyrrolidone with polyvinyl alchohol, which is commonly used for microneedles to create, gave the best combination between stiffness and stabilty.
A robotic arm inside the printer injects ink in microneedle moulds. A vacuum chamber beneath the mold suctions the ink to the bottom. This ensures that the ink reaches the tip of the needles. The molds need to be dried for a few days after they are filled. The prototype currently can produce 100 patches within 48 hours. However, the researchers believe that future versions will be able to produce more.
To test for long-term stability, the researchers created an ink with luciferase – a fluorescent luciferase – encoded RNA. The researchers applied the microneedle patch to mice that had been stored at four degrees Celsius (room temperature) or 25 degrees C. for up to 6 months. One batch of particles was also stored at 37 degrees C for a month.
The patches produced a strong fluorescent reaction when applied to mice under all these conditions. In contrast, the fluorescent response produced by a traditional intramuscular injection of the fluorescent-protein-encoding RNA declined with longer storage times at room temperature.
The researchers tested their Covid-19 vaccine by vaccinating mouse with two doses, four weeks apart. They measured the mice’s antibody response to virus. Mice that were vaccinated using the microneedle patches had similar responses to mice that received a traditional injected vaccine. The team saw the same antibody response after vaccinating mice with microneedle patch that was stored at room temperatures for up to 3 months.
“This work is particularly exciting as it realizes the ability to produce vaccines on demand,” said translational medicine and chemical engineering Prof. Joseph DeSimone at Stanford University, who was not involved in the research. “With the possibility of scaling up vaccine manufacturing and improved stability at higher temperatures, mobile vaccine printers can facilitate widespread access to RNA vaccines.”
Researchers plan to adapt this process to produce vaccines made with proteins, inactivated virus or other types. The ink composition was key in stabilizing mRNA vaccines, but the ink can contain various types of vaccines or even drugs, allowing for flexibility and modularity in what can be delivered using this microneedle platform,” Jaklenec concluded.