Numerous vaccinations, such as those against whooping cough and hepatitis B, include bacteria or viral fragments. They also have adjuvants, which help the immune system react better to these parts.
Adjuvants often comprise aluminum salts or similar substances that elicit a broader immunological response. However, MIT researchers found that a tiny particle called a metal-organic framework (MOF) can also make the immune system react strongly. It does this by turning on toll-like receptors, like the body’s alarm system against germs.
In experiments with mice, researchers found that the MOF could package and carry a piece of the SARS-CoV-2 spike protein. When the MOF breaks down in cells, it also helps boost the immune response.
The work demonstrates that this structure could help create vaccines that elicit a potent immune response, even though further research is required to employ these particles in human vaccines, the researchers said.
Ana Jaklenec, a principal investigator at MIT‘s Koch Institute for Integrative Cancer Research and one of the senior authors of the new study, said, “Understanding how the drug delivery vehicle can enhance an adjuvant immune response could be very helpful in designing new vaccines.”
Robert Langer, an MIT professor, and Dan Barouch, a Harvard professor, along with Shahad Alsaiari, a former MIT postdoc, led a study published in Science Advances. They studied a type of MOF called ZIF-8 to understand how it activates the immune system. ZIF-8 is made of zinc and imidazole molecules arranged in a lattice. It has been shown to enhance immune responses, but the exact mechanism is now understood.
To understand this, the MIT team made a test vaccine with the SARS-CoV-2 protein inside ZIF-8 particles. Due to their small size—roughly 100 to 200 nanometers—these particles can enter the body’s lymph nodes directly or through immune cells.
The ZIF-8 particles degrade inside the cells, releasing the virus proteins. The imidazole components subsequently activate toll-like receptors (TLRs), which aid in initiating the immune response. Alsaiari explains it’s like having a secret team at the molecular level to carry parts of the COVID-19 virus to the immune system, where they trigger specific responses to make the vaccine work better.
After analyzing cells from the lymph nodes, it was found that mice given the ZIF-8 particles containing the viral protein strongly activated a TLR pathway called TLR-7. This led to more production of cytokines and molecules related to inflammation. Those immunized with these particles showed a far higher reaction to the viral protein than mice just given the protein.
According to Jaklenec, the nanoparticles not only deliver the protein in a more controlled manner but also act as an adjuvant due to their structure. This resulted in specific responses to the Covid protein and required less vaccine than using the protein alone.
The research demonstrates that ZIF-8 is a substance that can activate the immune system. However, more research is needed to ensure it’s safe and can be made on a large scale. If ZIF-8 isn’t used for vaccines, the study can still help create similar tiny particles for delivering vaccines, according to Jaklenec.
Vaccines usually have two parts: an antigen and an adjuvant. We can make vaccines stronger by designing tiny particles that can deliver antigens and activate immune pathways.
Creating a subunit vaccine for COVID-19 might be less expensive and more straightforward than creating an mRNA vaccine. The researchers add that this could aid in the global distribution of vaccines during pandemics.
This study highlights the promising role of ZIF-8 nanoparticles in enhancing vaccine potency. It underscores the potential of subunit vaccines as a cost-effective solution for global immunization efforts, especially during pandemics.
Journal reference:
- SHAHAD K. ALSAIARI, SEBA NADEEF et al., Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer. Science Advances. DOI: 10.1126/sciadv.adj6380.