MIT Researchers Discover Nanoparticles as Potential Vaccine Adjuvants
In the race to develop effective vaccines against COVID-19, researchers at MIT have made a groundbreaking discovery that could revolutionize vaccine design. A team of scientists has found that nanoparticles called metal organic frameworks (MOFs) can provoke a strong immune response, acting as adjuvants to boost the body’s defense against pathogens. The findings, published in the journal Science Advances, have significant implications for the development of future vaccines.
Adjuvants are molecules that are often included in vaccines to enhance the immune system’s response to viral or bacterial proteins. Traditionally, adjuvants consist of aluminum salts or other molecules that trigger a nonspecific immune response. However, the MIT researchers have now shown that MOFs, specifically a type called ZIF-8, can also activate the innate immune system by interacting with toll-like receptors (TLRs) on cell proteins.
To investigate the mechanism behind this immune activation, the scientists created an experimental vaccine using ZIF-8 particles encapsulating the receptor-binding protein (RBD) of the SARS-CoV-2 virus. These particles, measuring between 100 and 200 nanometers in diameter, can enter the body’s lymph nodes directly or through immune cells.
Once inside the cells, the MOFs break down, releasing the viral proteins. The imidazole components of ZIF-8 then activate TLRs, which stimulate the innate immune response. This process effectively transports essential elements of the virus to the immune system, triggering specific immune responses that enhance vaccine efficacy.
The researchers found that mice vaccinated with ZIF-8 particles carrying the viral protein exhibited a significantly stronger immune response compared to those that received the protein alone. RNA sequencing of cells from the lymph nodes revealed that these particles strongly activated a TLR pathway known as TLR-7, leading to increased production of cytokines and other inflammation-related molecules.
“This process is analogous to establishing a covert operative team at the molecular level to transport essential elements of the Covid-19 virus to the body’s immune system, where they can activate specific immune responses to boost vaccine efficacy,” explains Shahad Alsaiari, lead author of the study.
While the study demonstrates the immunogenic ability of ZIF-8 particles, further research is needed to evaluate their safety and scalability for large-scale manufacturing. However, if ZIF-8 is not developed as a vaccine carrier, the findings from this study can guide researchers in developing similar nanoparticles for delivering subunit vaccines.
Subunit vaccines, which consist of an antigen and an adjuvant, are usually easier and cheaper to manufacture than mRNA vaccines. This advantage could facilitate broader access to vaccines, especially during times of pandemic. “Designing new vaccines that utilize nanoparticles with specific chemical moieties which aid in antigen delivery and activate particular immune pathways have the potential to enhance vaccine potency,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research.
The implications of this research extend beyond COVID-19. The use of MOFs as adjuvants could revolutionize vaccine design and pave the way for more effective vaccines against a range of diseases. By understanding how drug delivery vehicles enhance immune responses, scientists can develop novel vaccines that elicit specific and robust immune reactions.
The study was funded by Ibn Khaldun Fellowships for Saudi Arabian Women and the Koch Institute Support Grant from the U.S. National Cancer Institute. While more research is needed, this breakthrough discovery brings us one step closer to developing safer, more potent vaccines that can protect populations worldwide.
