(Nanowerk News) Giving vaccines to people who need them is not always easy. Many vaccines require cold storage, making it difficult to ship them to remote areas that do not have the necessary infrastructure.
MIT researchers have come up with a possible solution to this problem: a mobile vaccine printer that can be upgraded to produce hundreds of vaccine doses a day. This type of printer, which can be placed on a table, could be used anywhere a vaccine is needed, the researchers said.
“One day we could have on-demand vaccine production,” said Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “If, for example, there is an Ebola outbreak in a certain area, someone can send some of these printers over there and vaccinate people in that location.”
The printer produces a patch with hundreds of microneedles containing the vaccine. Patches can be placed on the skin, allowing the vaccine to dissolve without the need for a traditional injection. Once printed, vaccine patches can be stored for months at room temperature.
In a study appearing today in Natural Biotechnology (“Microneedle vaccine printer for thermostable COVID-19 mRNA vaccines”), the researchers demonstrated that they could use a printer to produce a thermostable Covid-19 RNA vaccine that could induce an immune response comparable to that produced by injected RNA vaccines, in mice.
Jaklenec and Robert Langer, David H. Koch Institute Professor at MIT and member of the Koch Institute, are senior authors of the study. The paper’s lead authors are former MIT postdoc Aurelien vander Straeten, former MIT graduate student Morteza Sarmadi ’21, and postdoc John Daristotle.
Most vaccines, including mRNA vaccines, must be refrigerated while in storage, making them difficult to stockpile or ship to locations where temperatures cannot be maintained. In addition, they require syringes, needles and trained healthcare professionals to manage them.
To overcome this obstacle, the MIT team looked for ways to produce vaccines on demand. Their initial motivation, before Covid-19 came around, was to build a device that could quickly manufacture and deploy vaccines during an outbreak of a disease like Ebola. Such devices could be shipped to remote villages, refugee camps, or military bases to enable rapid vaccination of large numbers of people.
Instead of producing traditional injectable vaccines, the researchers decided to work with a new type of vaccine delivery based on thumbnail-sized patches, which contain hundreds of microneedles. Such vaccines are now being developed for many diseases, including polio, measles, and rubella. When the patch is applied to the skin, the needle tip dissolves under the skin, releasing the vaccine.
“When Covid-19 started, concerns about vaccine stability and vaccine access motivated us to try to insert an RNA vaccine into the microneedle patch,” said Daristotle.
The “ink” the researchers used to print the vaccine-containing microneedles includes vaccine RNA molecules encapsulated in lipid nanoparticles, which help them remain stable for long periods of time.
Inks also contain polymers that can easily be formed into precise shapes and then remain stable for weeks or months, even when stored at room temperature or higher. The researchers found that the 50/50 combination of polyvinylpyrrolidone and polyvinyl alcohol, both of which are commonly used to form microneedles, had the best combination of stiffness and stability.
Inside the printer, a robotic arm injects ink into the microneedle die, and a vacuum beneath the die sucks the ink down to the bottom, ensuring it reaches the tip of the needle. Once the mold is filled, it takes a day or two for it to dry. The current prototype can produce 100 patches in 48 hours, but the researchers anticipate that future versions may be designed to have even higher capacities.
To test the vaccine’s long-term stability, the researchers first created an ink containing the RNA encoding luciferase, a fluorescent protein. They applied the resulting microneedle patches to mice after they had been stored at 4 degrees Celsius or 25 degrees Celsius (room temperature) for up to six months. They also stored one batch of particles at 37 degrees Celsius for one month.
Under all of these storage conditions, the patch induced a strong fluorescent response when applied to mice. In contrast, the fluorescent response elicited by traditional intramuscular injection of fluorescent protein-coding RNA decreased with longer storage times at room temperature.
Then, the researchers tested their microneedle Covid-19 vaccine. They vaccinated the mice with two doses of the vaccine, four weeks apart, then measured their antibody response to the virus. Mice vaccinated with the microneedle patch had a similar response to mice vaccinated with traditional injectable RNA vaccines.
The researchers also saw the same strong antibody response when they vaccinated mice with microneedle patches that had been stored at room temperature for up to three months.
“This work is very exciting because it realizes the ability to produce vaccines on demand,” said Joseph DeSimone, a professor of translational medicine and chemical engineering at Stanford University, who was not involved in the research. “With increased vaccine manufacturing possibilities and increased stability at higher temperatures, mobile vaccine printers can facilitate widespread access to RNA vaccines.”
While this research focuses on COVID-19 RNA vaccines, researchers plan to adapt the process to produce other types of vaccines, including vaccines made from inactivated proteins or viruses.
“Ink composition is key in stabilizing mRNA vaccines, but such inks can contain different types of vaccines or even drugs, allowing for flexibility and modularity in what can be delivered using these microneedle platforms,” said Jaklenec.