The printer produces patches with hundreds of microneedles containing vaccine. The patch can be attached to the skin, allowing the vaccine to dissolve without the need for a traditional injection. Credit: Ana Jaklenec and team/MIT
Needing to keep the very first COVID-19 vaccines at an ultra-low temperature—complete with specially designed boxes by Pfizer—opened many eyes to the struggles of the vaccine cold chain. But for scientists, it was nothing new.
Scientists, researchers, doctors and activists have worked for years to develop ways to ensure life-saving vaccines are delivered and stored properly to remote countries with low resources. Oftentimes, these are the same countries that need the vaccines the most as they are hit with disease outbreak after outbreak.
In 2018 and early 2019, researchers at MIT were looking for ways to fix the cold chain problem by developing “vaccines on-demand.” They wanted to build a device—a printer of sorts—that could quickly produce and deploy vaccines during outbreaks of diseases. Such a device could be shipped to a remote village, a refugee camp, or military base to enable rapid vaccination of large numbers of people.
“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,” said Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “We could someday have on-demand vaccine production.”
Printing vaccines
Instead of producing traditional injectable vaccines, the researchers decided to work with a novel type of vaccine delivery based on patches about the size of a thumbnail, which contain hundreds of microneedles. When the patch is applied to the skin, the tips of the needles dissolve under the skin, releasing the vaccine. Once the COVID-19 pandemic started, the team pivoted their original research to incorporate RNA vaccines into microneedle patches.
Inside the printer the MIT researchers developed, a robotic arm injects ink into the microneedle molds. A vacuum chamber below the mold then sucks the ink down to the bottom, making sure the ink reaches all the way to the tips of the needles. Once the molds are filled, they take a day or two to dry.
The “ink” used to print the vaccine-containing microneedles includes RNA vaccine molecules that are encapsulated in lipid nanoparticles, which help them to remain stable for long periods of time. The ink also contains polymers that can be easily molded into the right shape and then remain stable for weeks or months, even when stored at room temperature or higher. According to the study, researchers found that a 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.
Once printed, the vaccine patches can be stored for months at room temperature. The current prototype can produce 100 patches in 48 hours, but the researchers anticipate that future versions could be designed to have higher capacity.
Stability and efficacy
To test the long-term stability of the vaccines, the researchers applied microneedle patches to mice after the drugs had been stored in three different ways: at 4°C for 6 months; 25°C for 6 months; and 37°C for one month. The microneedle patches showed an immune response under all three conditions. In contrast, the traditional intramuscular injection showed declining response with longer storage times at room temperate (25°C).
With stability established, the researchers turned their attention to the efficacy of their COVID-19 microneedle vaccine. They vaccinated mice with two doses of the vaccine, four weeks apart, then measured the antibody response.
Mice vaccinated with the microneedle patch had a similar response to mice vaccinated with a traditional injected RNA vaccine. 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.
Given the success of the COVID-19 RNA vaccines, the research team said they plan to adapt the process to produce other types of vaccines, including those made from proteins or inactivated viruses.
“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,” said Jaklenec.