Many vaccines, including vaccines for hepatitis B and whooping cough, consist of fragments of viral or bacterial proteins. These vaccines often include other molecules called adjuvants, which help to boost the immune system’s response to the protein.
In a study of mice, the researchers showed that this MOF could successfully encapsulate and deliver part of the SARS-CoV-2 spike protein, while also acting as an adjuvant once the MOF is broken down inside cells.
While more work would be needed to adapt these particles for use as vaccines, the study demonstrates that this type of structure can be useful for generating a strong immune response, the researchers say.
“Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the new study.
Robert Langer, an MIT Institute Professor and member of the Koch Institute, and Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School, are also senior authors of the paper, which appears in Science Advances. The paper’s lead author is former MIT postdoc and Ibn Khaldun Fellow Shahad Alsaiari.
Immune activation
In this study, the researchers focused on a MOF called ZIF-8, which consists of a lattice of tetrahedral units made up of a zinc ion attached to four molecules of imidazole, an organic compound. Previous work has shown that ZIF-8 can significantly boost immune responses, but it wasn’t known exactly how this particle activates the immune system.
To try to figure that out, the MIT team created an experimental vaccine consisting of the SARS-CoV-2 receptor-binding protein (RBD) embedded within ZIF-8 particles. These particles are between 100 and 200 nanometers in diameter, a size that allows them to get into the body’s lymph nodes directly or through immune cells such as macrophages.
Once the particles enter the cells, the MOFs are broken down, releasing the viral proteins. The researchers found that the imidazole components then activate toll-like receptors (TLRs), which help to stimulate the innate immune response.
“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,” Alsaiari says.
RNA sequencing of cells from the lymph nodes showed that mice vaccinated with ZIF-8 particles carrying the viral protein strongly activated a TLR pathway known as TLR-7, which led to greater production of cytokines and other molecules involved in inflammation.
Mice vaccinated with these particles generated a much stronger response to the viral protein than mice that received the protein on its own.
“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,” Jaklenec says. “We were able to achieve very specific responses to the COVID protein, and with a dose-sparing effect compared to using the protein by itself to vaccinate.”
Vaccine access
While this study and others have demonstrated ZIF-8’s immunogenic ability, more work needs to be done to evaluate the particles’ safety and potential to be scaled up for large-scale manufacturing. If ZIF-8 is not developed as a vaccine carrier, the findings from the study should help to guide researchers in developing similar nanoparticles that could be used to deliver subunit vaccines, Jaklenec says.
“Most subunit vaccines usually have two separate components: an antigen and an adjuvant,” Jaklenec says. “Designing new vaccines that utilize nanoparticles with specific chemical moieties which not only aid in antigen delivery but can also activate particular immune pathways have the potential to enhance vaccine potency.”
One advantage to developing a subunit vaccine for COVID-19 is that such vaccines are usually easier and cheaper to manufacture than mRNA vaccines, which could make it easier to distribute them around the world, the researchers say.
“Subunit vaccines have been around for a long time, and they tend to be cheaper to produce, so that opens up more access to vaccines, especially in times of pandemic,” Jaklenec says.
More information: Shahad Alsaiari et al, Zeolitic Imidazolate Frameworks Activate Endosomal Toll-like Receptors and Potentiate Immunogenicity of SARS-CoV-2 Spike Protein Trimer, Science Advances (2024). DOI: 10.1126/sciadv.adj6380. www.science.org/doi/10.1126/sciadv.adj6380
Journal information: Science Advances
Provided by Massachusetts Institute of Technology

News
The CDC buried a measles forecast that stressed the need for vaccinations
This story was originally published on ProPublica, a nonprofit newsroom that investigates abuses of power. Sign up to receive our biggest stories as soon as they’re published. ProPublica — Leaders at the Centers for Disease Control and Prevention [...]
Light-Driven Plasmonic Microrobots for Nanoparticle Manipulation
A recent study published in Nature Communications presents a new microrobotic platform designed to improve the precision and versatility of nanoparticle manipulation using light. Led by Jin Qin and colleagues, the research addresses limitations in traditional [...]
Cancer’s “Master Switch” Blocked for Good in Landmark Study
Researchers discovered peptides that permanently block a key cancer protein once thought untreatable, using a new screening method to test their effectiveness inside cells. For the first time, scientists have identified promising drug candidates [...]
AI self-cloning claims: A new frontier or a looming threat?
Chinese scientists claim that some AI models can replicate themselves and protect against shutdown. Has artificial intelligence crossed the so-called red line? Chinese researchers have published two reports on arXiv claiming that some artificial [...]
New Drug Turns Human Blood Into Mosquito-Killing Weapon
Nitisinone, a drug for rare diseases, kills mosquitoes when present in human blood and may become a new tool to fight malaria, offering longer-lasting, environmentally safer effects than ivermectin. Controlling mosquito populations is a [...]
DNA Microscopy Creates 3D Maps of Life From the Inside Out
What if you could take a picture of every gene inside a living organism—not with light, but with DNA itself? Scientists at the University of Chicago have pioneered a revolutionary imaging technique called volumetric DNA microscopy. It builds [...]
Scientists Just Captured the Stunning Process That Shapes Chromosomes
Scientists at EMBL have captured how human chromosomes fold into their signature rod shape during cell division, using a groundbreaking method called LoopTrace. By observing overlapping DNA loops forming in high resolution, they revealed that large [...]
Bird Flu Virus Is Mutating Fast – Scientists Say Our Vaccines May Not Be Enough
H5N1 influenza is evolving rapidly, weakening the effectiveness of existing antibodies and increasing its potential threat to humans. Scientists at UNC Charlotte and MIT used high-performance computational modeling to analyze thousands of viral protein-antibody interactions, revealing [...]
Revolutionary Cancer Vaccine Targets All Solid Tumors
The method triggers immune responses that inhibit melanoma, triple-negative breast cancer, lung carcinoma, and ovarian cancer. Cancer treatment vaccines have been in development since 2010, when the first was approved for prostate cancer, followed [...]
Scientists Uncover Hidden Protein Driving Autoimmune Attacks
Scientists have uncovered a critical piece of the puzzle in autoimmune diseases: a protein that helps release immune response molecules. By studying an ultra-rare condition, researchers identified ArfGAP2 as a key player in immune [...]
Mediterranean neutrino observatory sets new limits on quantum gravity
Quantum gravity is the missing link between general relativity and quantum mechanics, the yet-to-be-discovered key to a unified theory capable of explaining both the infinitely large and the infinitely small. The solution to this [...]
Challenging Previous Beliefs: Japanese Scientists Discover Hidden Protector of Heart
A Japanese research team found that the oxidized form of glutathione (GSSG) may protect heart tissue by modifying a key protein, potentially offering a novel therapeutic approach for ischemic heart failure. A new study [...]
Millions May Have Long COVID – So Why Can’t They Get Diagnosed?
Millions of people in England may be living with Long Covid without even realizing it. A large-scale analysis found that nearly 10% suspect they might have the condition but remain uncertain, often due to [...]
Researchers Reveal What Happens to Your Brain When You Don’t Get Enough Sleep
What if poor sleep was doing more than just making you tired? Researchers have discovered that disrupted sleep in older adults interferes with the brain’s ability to clean out waste, leading to memory problems [...]
How to prevent chronic inflammation from zombie-like cells that accumulate with age
In humans and other multicellular organisms, cells multiply. This defining feature allows embryos to grow into adulthood, and enables the healing of the many bumps, bruises and scrapes along the way. Certain factors can [...]
Breakthrough for long Covid patients who lost sense of smell
A breakthrough nasal surgery has restored the sense of smell for a dozen long Covid patients. Experts at University College London Hospitals NHS Foundation Trust successfully employed a technique typically used for correcting blocked nasal passages, [...]