Researchers from the lab of Robert Langer, ScD, at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), say they have developed a printer for microneedle patches smaller than postage stamps that penetrate the skin to deliver vaccines, including the COVID-19 mRNA vaccine.

The research article, “A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines,” was published in Nature Biotechnology.

“We hope the systems and principles developed in our Nature Biotechnology paper to create a mobile vaccine printer will someday enable people in remote areas to receive vaccines on demand,” Langer told GEN. “We also hope this new way of creating microneedle patches as well as the new ways of stabilizing vaccines so that they will no longer have to be refrigerated will be further increase the utility of mRNA vaccines and other vaccines for people worldwide.”

In Case of Emergency

Senior author Ana Jaklenec, PhD, a research scientist and co-principal investigator in Langer’s lab, told GEN that this project predates the COVID-19 pandemic, when the research team was approached by the Biomedical Advanced Research and Development Authority (BARDA) to develop technologies that enable on-demand access to vaccines in case of a pandemic-type setting because they didn’t want to stockpile vaccines.

“The idea was that you could, in an emergency situation, deploy some of these printers and locally vaccinate the population to prevent the global spread of infection,” Jaklenec said. “These microneedle patch printers could be deployed to refugee camps or when a lot of people are all suddenly grouped together, which can be susceptible to disease quickly spreading. They would also work well in military bases around the world where you have a smaller population in a confined area.”

Jaklenec said that these vaccine-containing microneedle patches would be well suited for natural disaster responses, such as the recent earthquakes in Turkey. “We thought this would be a way to do this because you wouldn’t need the syringe or a specially trained healthcare worker,” said Jaklenec. “You could print [the microneedles] with the ink that has the vaccine in it and address some of these points that [BARDA] brought up because they could be self-administered in those kinds of circumstances.”

Microneedle pioneer Mark Prausnitz, PhD, Regents’ Professor, J. Erskine Love Jr. chair in chemical and biomolecular engineering and director of the Center for Drug Design, Development, and Delivery at Georgia Tech, told GEN, “Microneedle patches offer the promise of increasing access to vaccines by simplifying their storage, distribution, and administration. This study shows how to further increase access by enabling microneedle patch production on-demand and on-location.”

These microneedle patches are smaller than a square centimeter and can be self-administered anywhere on your arm or leg—essentially anywhere [on the skin]. Jaklenec said that, for mice, the patches have been made with 12 needles on the [microneedle patches], and, for humans, they often contain around 100 needles.

The vaccine “ink” was composed of lipid nanoparticles (LNPs) loaded with mRNA and a dissolvable polymer blend, and the resulting microneedle patches were shown to be shelf stable for at least six months at room temperature. Mice that were given printed microneedle patches with mRNA that coded for the SARS-CoV-2 spike protein receptor-binding domain had immune responses that were similar to those that were given directly into the muscle.

Beyond Nucleic Acid Vaccines

While this research primarily looked at mRNA vaccines, the dissolvable microneedle vaccine “ink” isn’t limited to nucleic acids. Prausnitz said that microneedle patches have been developed and studied in clinical trials for a number of different drugs and vaccines, including influenza, measles, and rubella vaccines. “This study builds on limited prior work on mRNA and COVID vaccination by microneedle patch to further expand the scope of microneedle patch vaccination into this important new area,” said Prausnitz.

When Jaklenec and researchers in the Langer lab started this project, the discussions with BARDA primarily revolved around Ebola and anthrax vaccines. This program was active when the pandemic hit, so Jaklenec and colleagues decided to switch gears slightly and focus on mRNA-based vaccines, which are very hard to stabilize. “You could use all types of vaccines, from inactivated whole vaccines to recombinant protein-based vaccines to DNA vaccines,” said Jaklenec. “Perhaps some of the live vaccines will be a little more challenging. Nonetheless, you could work on the formulation to see if you could stabilize them as well.”

Jaklenec thinks that it shouldn’t be too difficult to make the printers for these dissolvable microneedle-based vaccines and share them with scientists in many different places where the requisite laboratories are hard to come by. According to Jaklenec, the rate-limiting factor for bringing the device into these scenarios is a matter of resources. “As we’ve seen with the [COVID-19] pandemic, if there’s the will and financial resources to enable that will, things can move very quickly,” said Jaklenec. “We’re talking with companies and others to see if we can have partnerships in place that would help develop a commercial-based printer that could be distributed and then tested in different parts of the world.”

Jaklenec, Langer, and some of the article’s authors are listed as inventors on a pending patent application (17/903586) related to the described technology.