Mobile vaccine printers could enable rapid vaccination of large numbers of people

Getting vaccines to people who need them is not always easy. Many vaccines require refrigerated storage, making them difficult to ship to remote areas without the necessary infrastructure.

Researchers at MIT have come up with a possible solution to this problem. It’s his mobile vaccine printer that can be scaled up to produce hundreds of doses of vaccine per day. This kind of printer, which fits on a tabletop, could be deployed anywhere a vaccine is needed, researchers say.

One day, we may be able to produce vaccines on demand. For example, if there is an Ebola epidemic in a particular area, we can ship a few of these printers to that area to vaccinate the people there. ”

Ana Jaklenec, Massachusetts Institute of Technology Koch Institute for Integrative Cancer Research Fellow

The printer creates patches with hundreds of microneedles containing vaccines. The patch can be applied to the skin and dissolve the vaccine without the need for traditional injections. Printed vaccine patches can be stored at room temperature for several months.

In a study published today nature biotechnology, researchers have shown that a printer can be used to produce a heat-stable Covid-19 RNA vaccine. This could induce immune responses comparable to those generated by RNA vaccines injected in mice.

Jaklenec and MIT’s David H. Koch Institute professor and Koch Institute member Robert Langer are senior authors of the study. The lead authors of this paper are former MIT postdoc Aurelien vander Straeten, former MIT graduate student Morteza Sarmadi ’21, and postdoc John Daristotle.

vaccine printing

Most vaccines, including mRNA vaccines, require refrigeration during storage, making them difficult to stockpile or ship to locations where their temperature cannot be maintained. , and a trained medical professional is required.

To get around this obstacle, the MIT team set out to find a way to manufacture the vaccine on demand. Their original motivation, before the arrival of Covid-19, was to build devices that could rapidly manufacture and deploy vaccines during outbreaks of diseases such as Ebola. Such devices would be shipped to remote villages, refugee camps, or military bases, enabling rapid vaccination of large numbers of people.

Instead of manufacturing traditional injectable vaccines, researchers decided to use a new type of vaccine delivery based on thumbnail-sized patches containing hundreds of microneedles. Such vaccines are currently in development against many diseases, including polio, measles and rubella. When the patch is applied to the skin, the tip of the needle melts under the skin and 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 says.

The “ink” that researchers use to print vaccine-containing microneedles contains RNA vaccine It is a molecule encapsulated in lipid nanoparticles that helps keep it stable for a long time.

The ink also contains a polymer that can be easily molded into the correct shape and remains stable for weeks or months, even when stored at room temperature or higher. The researchers found that a 50/50 combination of polyvinylpyrrolidone and polyvinyl alcohol, both of which are commonly used to form microneedles, provided the best combination of stiffness and stability.

Inside the printer, a robotic arm injects ink into a microneedle mold, and a vacuum chamber under the mold sucks the ink to the bottom, allowing it to reach the tip of the needle. Once the mold is full, it will take a day or two to dry. The current prototype allows him to generate 100 patches in 48 hours, but researchers expect future versions may be designed with higher capacities.

antibody reaction

To test the vaccine’s long-term stability, researchers first created an ink containing RNA that encodes the fluorescent protein luciferase. The resulting microneedle patches were stored at 4 degrees Celsius or 25 degrees Celsius (room temperature) for up to 6 months before being applied to mice. They also stored one batch of particles at 37 degrees Celsius for one month.

Under all these storage conditions, application of the patch to mice elicited a strong fluorescent response. In contrast, the fluorescence response generated by conventional intramuscular injection of RNA encoding fluorescent proteins decreased with longer storage times at room temperature.

Next, researchers tested a Covid-19 microneedle vaccine. They vaccinated the mouse two times, four weeks apart, and measured the antibody response to the virus. Mice vaccinated with the microneedle patch responded similarly to mice vaccinated with a conventional injectable RNA vaccine.

The researchers also confirmed the same strong antibody response when mice were vaccinated with microneedle patches that had been stored at room temperature for up to three months.

“This research is particularly exciting because it enables the ability to produce vaccines on demand,” said Joseph Decimon, professor of translational medicine and chemical engineering at Stanford University. He was not involved in the research. can.”

Although this study focused on a Covid-19 RNA vaccine, the researchers hope to adapt the process to produce other types of vaccines, including vaccines made from proteins or inactivated viruses. I am planning.

“While the ink composition was critical in stabilizing the mRNA vaccine, the ink can contain many different types of vaccines and drugs, giving us the flexibility and modularity of what can be delivered using this microneedle platform. We make it possible,” says Jaklenec.

Other authors of this paper are Maria Kanelli, Lisa Tostanoski, Joe Collins, Apurva Pardeshi, Jooli Han, Dhruv Varshney, Behnaz Eshaghi, Johnny Garcia, Timothy Forster, Gary Li, Nandita Menon, Sydney Pyon, Linzixuan Zhang, Catherine Jacob- Dolan, Olivia Powers, Kevin Hall, Shahad Al-Siari, Morris Wolfe, Mark Tibbitt, Robert Farah, Dan Baluch.

This study was funded by the Biomedical Advanced Research and Development Authority (BARDA), Belgian American Educational Foundation, Wallonia-Brussels International, Bodossaki Foundation, Onassis Foundation, National Institutes of Health, and Koch Institute Support (core) Grant. From the National Cancer Institute.