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New nanoparticle to deliver vaccines and generate strong immune responses at lower dose

MOF activates the innate immune system through TLRs to provoke strong immune responses
- PMLiVE

Researchers from the Massachusetts Institute of Technology (MIT) have revealed that a new type of nanoparticle could be used to improve the delivery and immune responses of vaccines.

The study showed how metal-organic particles can deliver vaccines and act as an adjuvant to generate strong immune responses at a lower dose.

Currently, most vaccines consist of fragments of viral or bacterial proteins, as well as other molecules called adjuvants, which involve aluminium salts or other molecules to provoke nonspecific immune responses.

MIT researchers have shown, using mouse models, that a new type of nanoparticle known as a metal organic framework (MOF) can induce a strong immune response by activating the innate immune system through cell proteins called toll-like receptors (TLRs).

The study focused on a MOF called ZIF-8, which is a lattice of tetrahedral units made up of a zinc ion attached to four molecules of an organic compound called imidazole.

After creating an experimental vaccine consisting of the SARS-CoV-2 receptor-binding protein embedded within ZIF-8, the MOFs were broken down after entering the cells, releasing viral proteins.

Researchers found that imidazole components activated TLRs, which helped stimulate the innate immune response.

In mice vaccinated with ZIF-8 particles carrying the viral protein, a TLR pathway known as TLR-7 was strongly activated, which led to a significant production of cytokines and other molecules involved in inflammation.

Researchers discovered that mice vaccinated with these particles generated a strong response to the viral protein in comparison to mice that received the protein on its own.

ZIF-8, if not developed as a vaccine carrier, should help guide researchers when developing similar nanoparticles that could be used to deliver subunit vaccines, which are easier and cheaper to manufacture compared to mRNA vaccines.

Ana Jaklenec, principal investigator, MIT’s Koch Institute for Integrative Cancer Research, said: “Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines.”

“Vaccines that utilise nanoparticles with specific chemical moieties… not only aid in antigen delivery but can also activate particular immune pathways… [potentially enhancing] vaccine potency,” said Jaklenec.

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