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.

Most of these adjuvants consist of aluminum salts or other molecules that provoke a nonspecific immune response. A team of MIT researchers has now shown that a type of nanoparticle called a metal organic framework (MOF) can also provoke a strong immune response, by activating the innate immune system — the body’s first line of defense against any pathogen — through cell proteins called toll-like receptors.

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.

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.

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.

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.

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.

Sources:

Shahad K. Alsaiari, Seba Nadeef, John L. Daristotle, William Rothwell, Bujie Du, Johnny Garcia, Linzixuan Zhang, Morteza Sarmadi, Timothy A. Forster, Nandita Menon, Stacey Qiaohui Lin, Lisa H. Tostanoski, Nicole Hachmann, Erika Yan Wang, John D. Ventura, Dan H. Barouch, Robert Langer, Ana Jaklenec. Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer. Science Advances, 2024; 10 (10) DOI: 10.1126/sciadv.adj6380

Massachusetts Institute of Technology. (2024, March 6). New type of nanoparticle makes vaccines more powerful. ScienceDaily. Retrieved March 11, 2024 from www.sciencedaily.com/releases/2024/03/240306150424.htm
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