(295b) Metal-Organic Frameworks for Vaccine Stabilization: A Translational and Mechanistic Study

The global share of vaccinated infants is nearly 90%, yet in the poorest 70 countries, less than 10% of 1-year-olds are fully vaccinated. This discrepancy is largely due to failures in the “cold chain,” which necessitates the uninterrupted refrigeration of vaccines from the moment of manufacture until administration. Cold chain failures result in significant vaccine losses globally, posing a humanitarian problem as well as an economic one: cold-chain logistics costs are estimated to reach $16.6B this year.

One interdisciplinary solution to the cold chain problem relies on Metal-organic frameworks (MOFs)--a class of highly tunable porous materials. Recently, some groups have shown that encapsulating biological macromolecules (e.g., proteins and viruses) within a MOF scaffold can impart heightened stability to guest molecules far beyond ambient temperatures, perhaps enabling vaccine storage and transport without refrigeration.

In this work, we report the synthesis and thermostability of Tetanus Toxoid encapsulated in a Zeolitic Imidazolate Framework (ZIF-8). The toxoid protein retains exceptional immunological activity upon release from the framework after aging at 60°C for 1 month (shown by ELISA). Because the current literature focuses primarily on model guests of little clinical interest, our work represents an important contribution as it provides evidence of improved stability by MOF encapsulation on a clinically relevant (and never-before reported) guest protein.

While this research is predominantly translational, we also utilize crystallographic, spectroscopic, and scattering techniques to unveil the mechanism of guest stabilization. Through a collaboration with the Advanced Photon Source at Argonne National Labs, we have analyzed these biocomposites with Small-Angle X-ray Scattering (SAXS) generated by a synchrotron radiation source. With our approach of scaled spectra subtraction, we are able to deduce structural properties (i.e., size and shape) of encapsulated guests while they are being heated in situ. These experiments have provided novel insights into the heightened stability afforded by MOF biocomposites, which appears to rely on the tight confinement of guest molecules within MOF cavities (thus preventing deformation and aggregation of proteins).