Researchers at MIT have developed a novel lipid nanoparticle (LNP) that promises to make mRNA vaccines more effective and potentially lower the cost per dose. In studies involving mice, the new LNP successfully generated an immune response equivalent to those achieved with existing, FDA-approved materials, but at roughly 1/100th of the typical dose.
Why This Matters
mRNA vaccines have proven highly effective against diseases like COVID-19, but their production can be costly. Reducing the required dosage while maintaining efficacy offers several benefits: lower manufacturing costs, potentially fewer side effects, and improved accessibility for global health initiatives.
The Science Behind the Innovation
Existing mRNA vaccines are encapsulated within LNPs – tiny, fatty spheres – to protect the fragile mRNA from degradation and facilitate its entry into cells. These particles typically comprise five key components: an ionizable lipid (crucial for vaccine strength), cholesterol, a helper phospholipid, a polyethylene glycol lipid, and mRNA. The MIT team focused on optimizing the ionizable lipid to improve delivery efficiency.
A Novel Design
The researchers designed and screened a library of new ionizable lipids, incorporating cyclic structures to enhance mRNA delivery and ester groups to improve biodegradability. Through multiple rounds of screening in mice, they identified a top-performing LNP, dubbed AMG1541. A key advantage of AMG1541 is its superior ability to overcome “endosomal escape” – a critical step where LNPs must break out of cellular compartments called endosomes to deliver their mRNA. The new particles also degrade more rapidly after delivering their cargo, potentially minimizing side effects.
Promising Results in Flu Vaccine Trials
To assess the real-world potential, the researchers utilized the AMG1541 LNP to deliver an mRNA influenza vaccine in mice. When compared to a flu vaccine employing SM-102, a lipid already approved for COVID-19 vaccines (used by Moderna), the new LNP consistently generated the same antibody response with only 1/100th of the dose.
Enhanced Immune Response and Potential for Rapid Vaccine Development
Further investigation revealed that the new LNPs are more effective at delivering their cargo to antigen-presenting cells – crucial immune cells that display foreign antigens to activate other immune cells (like B and T cells). Additionally, they tend to accumulate in lymph nodes, boosting interaction with the immune system. This could lead to more accurate and rapid development of seasonal flu vaccines, a significant advantage over traditional vaccine production timelines that often require manufacturing to begin nearly a year in advance.
Broader Applications
The researchers believe these nanoparticles could be adapted for vaccines targeting other infectious diseases, including COVID-19, HIV, and beyond. “We have found that they work much better than anything that has been reported so far. That’s why, for any intramuscular vaccines, we think that our LNP platforms could be used to develop vaccines for a number of diseases,” said Gupta, a Koch Institute research scientist.
The development of these new LNPs represents a significant step toward more affordable and accessible mRNA vaccines, paving the way for improved global health outcomes.
