Multiple usage of vaccine doses are usually needed to properly prime the immune system. Administering a single patient with multiple doses at different times is a tedious, time consuming procedure. So far we do not have a method to overcome this problem.
However, a research team from MIT's Koch Institute for Integrative Cancer Research, Prof. Robert Langer and Dr. Ana Jaklenec (Jakelenec Group) have been working on “self-boosting” vaccines for a decade now, motivated by the crisis of under-immunized children in some of the poorer countries of the world with no healthcare infrastructure. Thanks to the COVID-19 pandemic, curiosity about the underlying platform has piqued in First World nations where vaccination boosters now have personal everyday relevance.
They have developed a new method for administering multiple vaccine doses based on time-release microparticles. These microparticles can maintain and protect the vaccine doses inside the body and release them in the body at predetermined time points. The time point for the release can be programmed to mimic the same schedule patients need to get booster shots.
Therefore, by injecting a cocktail of these microparticles, each releasing the vaccine at the right dose and time, this method can deliver all shots with the first injection and eliminate the need for injecting vaccine doses multiple times. These microparticles are made from safe materials completely compatible with the human body and automatically dissolve over time in the body. In fact, these are fabricated from a biocompatible polymer called PLGA used to make resorbable sutures.
Polymers are long-chained molecules that might be thought of like long hair or spaghetti that gets tangled up, Dr Jakelenec says, and the PLGA variety is comprised of Lactic acid and Glycolic acid. Water eventually breaks the bond between those two building blocks. When enough of these polymers have broken down, the lid suddenly becomes porous and breaks apart, which is key to the pulsatile release of the contents.
Adjusting the lactic acid level up or down will, respectively, lengthen or shorten the time it takes for the water to cleave that bond and degrade the material. Other determinants of the release time point in the largely aqueous human body include the length of the chain, with longer chains having more bonds for water molecules to break. Each chain can also have a different end group which, if more hydrophobic, will take longer to degrade.
The main limitation to broad application of the drug/vaccine delivery approach would be dosing, Dr Jaklenec continues. “Whatever your normal dose is, you are also going to have the added mass of the polymer,” which could be tricky for anything requiring a “super-huge” dose.
Currently, researchers are injecting around 20 particle doses into a small animal model, she says. Human dosing for three different vaccines and three different boosters may require 200 or more particles depending on the dose, each smaller than a grain of sand.
The core-shell microparticles are nonetheless a true platform, Dr Jakelenec says, which can accommodate the mixing and matching of several vaccines together with their boosters as well as cancer drugs, hormone therapy, and biologics.
Any applications requiring multiple injections on a regular basis can potentially benefit from this technology. eg: Insulin.
The self-boosting polio vaccine continues to be tested in animal models. Excluding the newer mRNA varieties, polio is one of the most unstable of vaccines, says Dr Jaklenec. Temperature is the big challenge here, since the polio vaccine—which generally requires refrigeration—would need to be stored in the body at 37 degrees Celsius for many months.
Prototypes developed for three different versions of the polio vaccine have shown that one injection with the microparticles elicits the same neutralizing immune response in rats as giving them multiple shots, she reports. “Now that work is in non-human primates, and we hope soon to be able to do a small human trial.”
Finally another advantage is the handling of the vaccines. Traditional vaccines are in liquid form, hard to ship, and require low temperature for storage. Conversely, vaccines encapsulated in these self-boosting microparticles are dried and can be more easily shipped worldwide. When stored properly without exposure to humidity, these particles can improve vaccine shelf-life and maintain the encapsulated vaccine stable even at room temperature. This could potentially be a significant benefit to the global distribution of vaccines currently hampered by the cold chain issue.
However, a research team from MIT's Koch Institute for Integrative Cancer Research, Prof. Robert Langer and Dr. Ana Jaklenec (Jakelenec Group) have been working on “self-boosting” vaccines for a decade now, motivated by the crisis of under-immunized children in some of the poorer countries of the world with no healthcare infrastructure. Thanks to the COVID-19 pandemic, curiosity about the underlying platform has piqued in First World nations where vaccination boosters now have personal everyday relevance.
They have developed a new method for administering multiple vaccine doses based on time-release microparticles. These microparticles can maintain and protect the vaccine doses inside the body and release them in the body at predetermined time points. The time point for the release can be programmed to mimic the same schedule patients need to get booster shots.
Therefore, by injecting a cocktail of these microparticles, each releasing the vaccine at the right dose and time, this method can deliver all shots with the first injection and eliminate the need for injecting vaccine doses multiple times. These microparticles are made from safe materials completely compatible with the human body and automatically dissolve over time in the body. In fact, these are fabricated from a biocompatible polymer called PLGA used to make resorbable sutures.
Polymers are long-chained molecules that might be thought of like long hair or spaghetti that gets tangled up, Dr Jakelenec says, and the PLGA variety is comprised of Lactic acid and Glycolic acid. Water eventually breaks the bond between those two building blocks. When enough of these polymers have broken down, the lid suddenly becomes porous and breaks apart, which is key to the pulsatile release of the contents.
Adjusting the lactic acid level up or down will, respectively, lengthen or shorten the time it takes for the water to cleave that bond and degrade the material. Other determinants of the release time point in the largely aqueous human body include the length of the chain, with longer chains having more bonds for water molecules to break. Each chain can also have a different end group which, if more hydrophobic, will take longer to degrade.
The main limitation to broad application of the drug/vaccine delivery approach would be dosing, Dr Jaklenec continues. “Whatever your normal dose is, you are also going to have the added mass of the polymer,” which could be tricky for anything requiring a “super-huge” dose.
Currently, researchers are injecting around 20 particle doses into a small animal model, she says. Human dosing for three different vaccines and three different boosters may require 200 or more particles depending on the dose, each smaller than a grain of sand.
The core-shell microparticles are nonetheless a true platform, Dr Jakelenec says, which can accommodate the mixing and matching of several vaccines together with their boosters as well as cancer drugs, hormone therapy, and biologics.
Any applications requiring multiple injections on a regular basis can potentially benefit from this technology. eg: Insulin.
The self-boosting polio vaccine continues to be tested in animal models. Excluding the newer mRNA varieties, polio is one of the most unstable of vaccines, says Dr Jaklenec. Temperature is the big challenge here, since the polio vaccine—which generally requires refrigeration—would need to be stored in the body at 37 degrees Celsius for many months.
Prototypes developed for three different versions of the polio vaccine have shown that one injection with the microparticles elicits the same neutralizing immune response in rats as giving them multiple shots, she reports. “Now that work is in non-human primates, and we hope soon to be able to do a small human trial.”
Finally another advantage is the handling of the vaccines. Traditional vaccines are in liquid form, hard to ship, and require low temperature for storage. Conversely, vaccines encapsulated in these self-boosting microparticles are dried and can be more easily shipped worldwide. When stored properly without exposure to humidity, these particles can improve vaccine shelf-life and maintain the encapsulated vaccine stable even at room temperature. This could potentially be a significant benefit to the global distribution of vaccines currently hampered by the cold chain issue.
