A “smart” vaccine may be on the horizon as researchers develop microparticles that can release their contents at different time points, potentially streamlining the vaccination process.
Having previously created microparticles that act as vehicles for vaccine delivery, a group of researchers at the Massachusetts Institute of Technology (MIT; MA, USA) have conducted further investigations into the technique to reveal how the microparticles degrade to release their contents and how to stabilize the microparticle contents to ensure effective release. By creating and optimizing these microparticles, researchers offer an alternative delivery method for vaccines and other therapeutics, such as cancer drugs.
The MIT team originally built the microparticle, which resembles a coffee cup and lid, in 2017 out of the biocompatible polymer, PLGA. After filling the cup with the vaccine, the lids are sealed to the cup via heat fusing. The creation of these “cups” follows a technique called SEAL, StampEd Assembly of polymer Layers. Recently, the focus has shifted from the building of the cups to the mechanics underlying the release of the vaccine and the vaccines’ stability throughout this process.
“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,” reported senior author Ana Jaklenec. “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.”
A nanoparticle vaccine, providing protection from up to eight viral receptor binding domains, is set to enter Phase I clinical trials after promising results in preclinical studies.
Researchers discovered that the PLGA cups were gradually broken down by water, which caused the lid to become porous and eventually fall apart, releasing the contents of the cup. They also observed that vaccine release kinetics were not affected by microparticle size or shape; release timing was determined by the composition of the particle polymer and its associated chemical groups.
Another aspect to consider when developing these self-boosting vaccines is microparticle content stability. When the polymer eventually breaks down through contact with water, the byproducts are lactic acid and glycolic acid. These byproducts affect the pH of the surrounding environment, damaging the vaccines held in the microparticles. The research team is working on further adjustments to improve drug stability.
“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. 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,” senior author Robert Langer commented.
The team has already applied the microparticle technology to a polio vaccine, which was tested in animals. Because the polio vaccine would normally have to be administered in two or four different injections, the alternative microparticle delivery option could make immunization against polio virus more efficient and effective. In places where healthcare access is unreliable, this delivery method could be important for childhood vaccinations. Additionally, the team suggests that this technique could be used for delivering cancer drugs and hormone therapies in the future.
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