CAMBRIDGE, Mass. — A one-jab, self-boosting vaccine that provides patients with several doses at different times is currently under development.
Scientists from the Massachusetts Institute of Technology say the one-shot would provide multiple stages of vaccination thanks to microparticles that release payloads at different intervals. These microparticles resemble tiny coffee cups, sealed with a lid. The jab could combat a host of illnesses, from measles to COVID, according to the team.
The particles remain under the skin until the vaccine is released and then breaks down, just like dissolving stitches. They could be particularly useful for administering childhood vaccinations in regions where people do not have regular access to medical care. It also opens the door to delivering a range of other therapies including cancer drugs, hormone treatments, and other medications.
“This is a platform that can be broadly applicable to all types of vaccines, including recombinant protein-based vaccines, DNA-based vaccines, even RNA-based vaccines,” says senior study author Dr. Ana Jaklenec in a media release.
“Understanding the process of how the vaccines are released, which is what we described in this paper, has allowed us to work on formulations that address some of the instability that could be induced over time.”
How does the multi-dose shot work?
The particles are made from PLGA, a biocompatible polymer that has already been approved for use in medical devices such as implants, sutures, and prosthetic devices. The team at MIT’s Koch Institute for Integrative Cancer Research created arrays of silicon molds to shape the “cups” and “lids.”
Once assembled, the team used a custom-built, automated dispensing system to fill each cup with a drug or vaccine. After filling the cups, the lids are aligned and lowered onto each cup. The system is heated slightly until the cup and lid fuse together — sealing the drug inside. The technique called SEAL (StampEd Assembly of polymer Layers) can produce particles of any shape or size.
“We wanted to understand mechanistically what’s happening, and how that information can be used to help stabilize drugs and vaccines and optimize their kinetics,” Dr. Jaklenec adds.
An analysis of the release mechanism revealed the polymers are gradually cleaved by water. When enough have broken down, the lid becomes very porous. Very soon afterwards, the material breaks apart, allowing the contents to spill out.
“We realized that sudden pore formation prior to the release time point is the key that leads to this pulsatile release,” says PhD candidate and lead study author Morteza Sarmad. “We see no pores for a long period of time, and then all of a sudden we see a significant increase in the porosity of the system.”
A variety of design parameters – including size, shape, and composition of the polymers – affect the timing of drug release.
“If you want the particle to release after six months for a certain application, we use the corresponding polymer, or if we want it to release after two days, we use another polymer,” Sarmadi says. “A broad range of applications can benefit from this observation.”
Scientists still have some problems to work out
When water breaks them down, byproducts including lactic acid and glycolic acid make the environment more acidic. This can damage the drugs within, which usually contain proteins or nucleic acids. The researchers are now working on ways to counteract this effect and improve stability.
A computational model can predict how a particular particle will degrade. This could help to guide development of other microfabricated or 3D-printed particles and medical devices. A self-boosting polio vaccine is already under investigation in animals. Usually, patients receive the polio vaccine in a series of two to four separate injections.
“We believe these core shell particles have the potential to create a safe, single-injection, self-boosting vaccine in which a cocktail of particles with different release times can be created by changing the composition,” notes co-senior author Prof. Robert Langer.
“Such a single injection approach has the potential to not only improve patient compliance but also increase cellular and humoral immune responses to the vaccine.”
The method is already showing promise for treating diseases such as cancer. Two years ago, the researchers showed they could deliver drugs that stimulate a pathway called STING. In mice, it boosted immune responses. After being injected into tumors, the particles delivered several doses of the drug over several months — inhibiting growth and reducing spread of the disease.
The study is published in the journal Science Advances.
South West News Service writer Mark Waghorn contributed to this report.