Innovative Microparticles Enable Single-Injection Vaccines for Enhanced Immunization

Globally, approximately 20% of children remain under-immunized, resulting in 1.5 million preventable child deaths annually due to vaccine-preventable diseases. Among these under-immunized children, about half have received at least one vaccine dose but did not complete the full vaccination series, while the others received no vaccinations at all.

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To address this challenge, researchers at MIT are developing innovative microparticles capable of delivering their vaccine payload weeks or even months post-injection. This groundbreaking approach aims to create vaccines that require only a single administration, with multiple doses released at staggered intervals.

In a recent study published in the journal Advanced Materials, the team demonstrated the successful delivery of two doses of a diphtheria vaccine using these microparticles—one dose was released immediately, while the second was administered two weeks later. Remarkably, mice receiving this dual-dose regimen produced antibody levels comparable to those receiving two separate doses spaced two weeks apart.

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The researchers aspire to extend these dosing intervals, potentially revolutionizing the delivery of childhood vaccines that traditionally require several doses over a few months, such as the polio vaccine.

Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research, highlights the long-term vision of this research: “Our goal is to enhance vaccine accessibility, especially for children in remote regions with limited access to healthcare facilities, including rural areas in the United States and parts of developing countries.”

Jaklenec and her colleague Robert Langer, a prominent figure at MIT, serve as senior authors of the study, with Linzixuan (Rhoda) Zhang, an MIT graduate student who recently completed her PhD in chemical engineering, as the lead author.

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In recent years, Jaklenec, Langer, and their team have focused on vaccine delivery systems using PLGA—a polymer known for its biodegradable properties. In 2018, they demonstrated the effectiveness of these particles for delivering two doses of the polio vaccine approximately 25 days apart. However, one limitation of PLGA is that its gradual breakdown can create an acidic environment, potentially harming the encapsulated vaccine.

To tackle this issue, the MIT team is investigating alternative materials that maintain a neutral pH during degradation. The latest study shifts focus to polyanhydride, a biodegradable polymer developed by Langer over 40 years ago for drug delivery purposes. Polyanhydrides are hydrophobic and, as they degrade in the body, they produce less acidic byproducts.

For this research, the team created a library of 23 distinct polyanhydride polymers by varying the chemical structures and ratios of two different monomers. These polymers were assessed based on their thermal stability and their ability to withstand temperatures above 104°F (40°C), ensuring they remained stable throughout microparticle fabrication.

The particles were produced using a technique called stamped assembly of polymer layers (SEAL), which involves forming cup-shaped particles in silicon molds that are filled with the vaccine antigen and then sealed with a cap made from the same polymer. After rigorous testing, six top-performing candidates were identified for further development.

“While designed for single-injection vaccines, it can also adapt to deliver small molecules or biologics needing durability or multiple doses while accommodating drugs sensitive to acidity.”

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In addition to developing these innovative particles, the researchers employed machine-learning models to explore factors influencing particle degradation rates in vivo. They evaluated nearly 500 potential polymer configurations to predict release timings accurately and confirmed these predictions through controlled testing.

The ultimate goal is to extend the release interval of these delivery systems—potentially allowing for vaccination schedules that require multiple doses over years instead of months. As Zhang explains, “By increasing molecular weight or hydrophobicity, or through cross-linking modifications, we can manipulate the release kinetics and retention times of these particles.”

Looking ahead, the researchers plan to investigate using these delivery particles for additional vaccine types and other sensitive pharmaceuticals requiring precise dosing schedules. Jaklenec emphasizes the broad potential of this technology.

This pioneering research has received partial funding from the Koch Institute Support (core) Grant from the National Cancer Institute.