” We could at some point have on-demand vaccine production,” states Ana Jaklenec, a research study scientist at MITs Koch Institute for Integrative Cancer Research. “If, for instance, there was an Ebola break out in a particular area, one could deliver a few of these printers there and vaccinate the individuals because location.”
The printer produces spots with numerous microneedles containing vaccine. The spot can be attached to the skin, enabling the vaccine to dissolve without the need for a standard injection. Credit: Courtesy of the researchers
The printer produces spots with numerous microneedles including vaccine. The patch can be attached to the skin, enabling the vaccine to liquify without the requirement for a conventional injection. Once printed, the vaccine spots can be stored for months at space temperature level.
In a study that was published in Nature Biotechnology on April 24, 2023, the researchers revealed they might utilize the printer to produce thermostable Covid-19 RNA vaccines that might induce an equivalent immune action to that created by injected RNA vaccines, in mice.
Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, are the senior authors of the study. The papers lead authors are previous MIT postdoc Aurelien vander Straeten, Morteza Sarmadi PhD 22, and postdoc John Daristotle.
Printing vaccines
Most vaccines, consisting of mRNA vaccines, should be refrigerated while kept, making it challenging to stockpile them or send them to locations where those temperatures cant be maintained. Moreover, they require syringes, needles, and skilled health care experts to administer them.
To navigate this obstacle, the MIT group set out to find a way to produce vaccines as needed. Their original motivation, before Covid-19 got here, was to develop a gadget that could rapidly produce and release vaccines during outbreaks of diseases such as Ebola. Such a gadget could be shipped to a remote town, a refugee camp, or military base to enable quick vaccination of large numbers of people.
Inside the printer, a robotic arm injects ink into microneedle molds, and a vacuum chamber listed below the mold sucks the ink down to the bottom. Visualized is an example of the mold. Credit: Courtesy of the researchers
Rather of producing conventional injectable vaccines, the researchers decided to work with an unique kind of vaccine delivery based upon spots about the size of a thumbnail, which include hundreds of microneedles. Such vaccines are now in advancement for many diseases, including polio, measles, and rubella. When the patch is applied to the skin, the ideas of the needles dissolve under the skin, releasing the vaccine.
” When Covid-19 started, issues about vaccine stability and vaccine access inspired us to try to incorporate RNA vaccines into microneedle spots,” Daristotle states.
The “ink” that the researchers utilize to print the vaccine-containing microneedles consists of RNA vaccine particles that are encapsulated in lipid nanoparticles, which assist them to stay steady for long durations of time.
The ink also includes polymers that can be easily formed into the right shape and then stay stable for months or weeks, even when saved at space temperature or higher. The scientists discovered that a 50/50 mix of polyvinylpyrrolidone and polyvinyl alcohol, both of which are frequently utilized to form microneedles, had the very best mix of stiffness and stability.
Inside the printer, a robotic arm injects ink into microneedle molds, and a vacuum chamber below the mold sucks the ink down to the bottom, making sure that ink reaches all the method to the ideas of the needles. As soon as the molds are filled, they take a day or 2 to dry. The existing prototype can produce 100 spots in 48 hours, however the scientists prepare for that future variations might be designed to have higher capacity.
Antibody action
To evaluate the long-lasting stability of the vaccines, the researchers initially created an ink consisting of RNA that encodes luciferase, a luminescent protein. They applied the resulting microneedle spots to mice after being kept at either 4 degrees Celsius or 25 degrees Celsius (room temperature) for as much as six months. They likewise kept one batch of the particles at 37 degrees Celsius for one month.
Under all of these storage conditions, the spots caused a strong luminous reaction when used to mice. In contrast, the luminescent reaction produced by a standard intramuscular injection of the luminescent-protein-encoding RNA declined with longer storage times at space temperature level.
The researchers tested their Covid-19 microneedle vaccine. They vaccinated mice with 2 dosages of the vaccine, four weeks apart, then determined their antibody action to the virus. Mice immunized with the microneedle spot had a similar action to mice vaccinated with a traditional, injected RNA vaccine.
When they vaccinated mice with microneedle patches that had actually been kept at room temperature for up to three months, the scientists likewise saw the very same strong antibody response.
” This work is especially amazing as it realizes the capability to produce vaccines as needed,” states Joseph DeSimone, a professor of translational medicine and chemical engineering at Stanford University, who was not associated with the research study. “With the possibility of scaling up vaccine production and enhanced stability at higher temperature levels, mobile vaccine printers can facilitate widespread access to RNA vaccines.”
While this study focused on Covid-19 RNA vaccines, the researchers plan to adjust the procedure to produce other types of vaccines, including vaccines made from proteins or inactivated infections.
” The ink structure was key in stabilizing mRNA vaccines, but the ink can contain various types of vaccines or even drugs, allowing for versatility and modularity in what can be provided utilizing this microneedle platform,” Jaklenec states.
Reference: “A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines” by Aurélien vander Straeten, Morteza Sarmadi, John L. Daristotle, Maria Kanelli, Lisa H. Tostanoski, Joe Collins, Apurva Pardeshi, Jooli Han, Dhruv Varshney, Behnaz Eshaghi, Johnny Garcia, Timothy A. Forster, Gary Li, Nandita Menon, Sydney L. Pyon, Linzixuan Zhang, Catherine Jacob-Dolan, Olivia C. Powers, Kevin Hall, Shahad K. Alsaiari, Morris Wolf, Mark W. Tibbitt, Robert Farra, Dan H. Barouch, Robert Langer and Ana Jaklenec, 24 April 2023, Nature Biotechnology.DOI: 10.1038/ s41587-023-01774-z.
Other authors of the 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 Alsaiari, Morris Wolf, Mark Tibbitt, Robert Farra, and Dan Barouch.
The research was moneyed by the Biomedical Advanced Research and Development Authority (BARDA), the Belgian American Educational Foundation, Wallonia-Brussels International, the Bodossaki Foundation, the Onassis Foundation, the U.S. National Institutes of Health, and the Koch Institute Support (core) Grant from the National Cancer Institute.
MIT scientists have created a mobile vaccine printer that might be scaled as much as produce numerous vaccine doses in a day. This sort of printer, which can fit on a tabletop, could be deployed anywhere vaccines are needed. Pictured is an artists interpretation of the printer. Credit: Ryan Allen from Second Bay Studios
The printer creates vaccine-filled microneedle patches that can be kept long-term at room temperature level and applied to the skin.
Getting vaccines to people who require them isnt always simple. Many vaccines require cold storage, making it tough to deliver them to remote locations that do not have the needed infrastructure.
MIT researchers have created a possible solution to this problem: a mobile vaccine printer that could be scaled as much as produce hundreds of vaccine doses in a day. This type of printer, which can fit on a tabletop, might be released anywhere vaccines are needed, the researchers say.
MIT researchers have designed a mobile vaccine printer that might be scaled up to produce hundreds of vaccine doses in a day. The printer produces patches with hundreds of microneedles including vaccine. The printer produces spots with hundreds of microneedles containing vaccine. Rather of producing standard injectable vaccines, the scientists chose to work with an unique type of vaccine delivery based on spots about the size of a thumbnail, which consist of hundreds of microneedles. The researchers tested their Covid-19 microneedle vaccine.