Vaccinations are the safest way to protect against disease. However, many vaccines become ineffective when exposed to room temperature or heat. In less developed countries with undependable electricity, physicians struggle to administer fully effective vaccines because of breaks in the "cold chain" that supplies vaccines from manufacturers to patients. Even in more developed regions, 80 percent of the costs of manufacturing and distributing vaccines are associated with keeping them cold. These challenges prevent patients from accessing lifesaving immunizations and increase the risk of global pandemics.
During the 68th Annual Meeting of the American Crystallographic Association, being held July 20-24, 2018, in Toronto, Canada, Jeremiah Gassensmith, an assistant professor at the University of Texas at Dallas, will describe his lab's work developing metal-organic framework (MOF) vaccines. This new biocompatible polymer framework "freezes" proteins inside vaccines. The proteins then dissolve when injected in human skin. This innovation could help health care providers transport and administer vaccines in remote areas with unreliable power.
"MOF vaccines are crystals that contain an antigen like the protein on the surface of influenza, except they're frozen inside a crystalline lattice, so they can't denature or change shape," Gassensmith explained. MOFs contain clusters of metal ions bound together with organic links. The structure resembles building blocks and enables increased molecular control of pore size, shape and functionality.
Structural advantages of MOFs allow them to perform better at room temperature than artificial encasings like silica. Specifically, MOFs' porous structure allows them to function as a semipermeable barrier to transport biological matter like proteins or antigens in vaccines.
Furthermore, MOFs remain stable in many solvents, including water, but they dissolve in low-pH environments like human skin. This is an extra advantage for transdermal vaccine administration, because the skin contains immune cells that can help activate the vaccine and its acidity will help the MOF dissolve.
Researchers synthesize MOFs through a process called "biomimetic mineralization," based on the biomineralization process that forms natural materials like bones and shells. In biomimetic mineralization, researchers exploit how negative protein surfaces attract positive metal ions, so the MOF grows a protective shell around the vaccine.
Gassensmith was surprised to discover that their method effectively encapsulated hundreds of nanometer-wide inactivated viruses as well as small proteins such as insulin. "We were able to grow the shell on the surface of these very large protein ensembles just as effectively as we could on the smaller proteins," Gassensmith said. "It doesn't seem to matter how big or how small the structure is. We can encapsulate all of it."
Going forward, the team hopes to integrate their work into a clinic. "Our next phase is to increase the in vivo [in animals] work we are doing and create vaccines that might help target malaria," Gassensmith said.