A Scalable Synthesis of Adjuvanting Antigen Depots Based on Met-al-Organic Frameworks

Abstract

Vaccines have saved countless lives by preventing and even irradicating infectious dis-eases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immuno-genicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vac-cinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as op-posed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phe-nomenon is at least partly owed to the sustained release of OVA from the ZIF-8 composite, acting as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the hu-moral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a labora-tory setting, sufficient for up to 20,000 vaccine doses.

The Promise and Potential of Metal-Organic Frameworks and Covalent Organic Frameworks in Vaccine Nanotechnology

“…154 It is important to understand, however, that the FDAapproved adjuvant alum is more cytotoxic than ZIF-8 that the same approximate dose used to vaccinate mice would be used in humans, which are comparatively gigantic. 227 The material needed is typically only 10-50 µg of antigen, meaning the MOF needed is typically well below a milligram. Further, vaccines are not injected into the blood, and most of their degradation occurs at the injection site.…”