MIT breakthrough makes vaccines more powerful
Researchers at MITÂ have discovered a promising avenue for vaccine development, potentially revolutionizing the way we combat infectious diseases like COVID-19. (CREDIT: Creative Commons)
Researchers at MIT have discovered a promising avenue for vaccine development, potentially revolutionizing the way we combat infectious diseases like COVID-19. Their study, published in Science Advances, highlights the use of metal organic frameworks (MOFs) as a novel tool for vaccine delivery and immune response enhancement.
Traditionally, vaccines utilize fragments of viral or bacterial proteins to trigger an immune response. These vaccines often include adjuvants, additional molecules that enhance the immune system's reaction to the protein.
Most adjuvants currently used are aluminum salts or similar compounds that provoke a generalized immune response. However, MIT scientists have demonstrated that MOFs can also elicit a robust immune response by activating toll-like receptors, crucial proteins involved in the body's initial defense against pathogens.
TEM micrographs and simplified schematic of ZIF-8 (A) and GR-ZIF (B). (CREDIT: Science Advances)
Lead researcher Ana Jaklenec, from MIT's Koch Institute for Integrative Cancer Research, explains the significance of this discovery, stating, "Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines."
The study, led by former MIT postdoc Shahad Alsaiari, focused on a specific MOF known as ZIF-8. This MOF comprises a zinc ion and imidazole molecules arranged in a lattice structure.
By embedding fragments of the SARS-CoV-2 spike protein within ZIF-8 particles, researchers aimed to explore its immunogenic properties and its mechanism of action.
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Upon entering cells, these ZIF-8 particles degrade, releasing the viral proteins. The imidazole components then activate toll-like receptors, kickstarting the innate immune response.
Alsaiari compares this process to "establishing a covert operative team at the molecular level" to deliver essential elements of the virus to the immune system, thereby enhancing vaccine efficacy.
In experiments with mice, vaccination with ZIF-8 particles carrying viral proteins led to a significant activation of the toll-like receptor pathway, resulting in heightened production of cytokines and inflammation-related molecules. Notably, mice vaccinated with these particles exhibited a much stronger immune response compared to those receiving the viral protein alone.
PXRD patterns of simulated ZIF-8 and GR-ZIF, demonstrating the retained crystallinity of ZIF-8 after loading RBD trimer and Gdq. FTIR analyses of RBD trimer and GR-ZIF, indicating the adsorption of RBD trimer on the surface of ZIF-8. a.u., arbitrary units. (CREDIT: Science Advances)
Jaklenec emphasizes the dual role of ZIF-8 particles, stating, "Not only are we delivering the protein in a more controlled way through a nanoparticle, but the compositional structure of this particle is also acting as an adjuvant."
Despite these promising results, further research is needed to evaluate the safety and scalability of ZIF-8 particles for large-scale vaccine production. Jaklenec suggests that if ZIF-8 is not pursued as a vaccine carrier, the findings could inform the development of similar nanoparticles for delivering subunit vaccines.
Cumulative release profile of RBD trimer from GR-ZIF at physiological pH (7) and endosomal pH (5.5), demonstrating the pH responsive release from ZIF-8. TEM micrographs of GR-ZIF degradation over time in response to low pH (5.3). (CREDIT: Science Advances)
Subunit vaccines, which typically consist of an antigen and an adjuvant, offer advantages in terms of cost and ease of manufacturing compared to mRNA vaccines. Jaklenec highlights their potential for broader vaccine access, especially in the context of a global pandemic.
As scientists continue to explore innovative approaches to vaccine development, the study underscores the importance of leveraging nanotechnology to enhance vaccine potency and accessibility. With further advancements, MOFs like ZIF-8 could play a pivotal role in shaping the future of immunization strategies worldwide.
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