Zeolitic Imidazolate Framework Nanoencapsulation of CpG for Stabilization and Enhancement of Immunoadjuvancy
Olivia R. Brohlin, Ryanne N. Ehrman, Fabian C. Herbert, Yalini H. Wijesundara, Arun Raja, Arezoo Shahrivarkevishahi, Shashini D. Diwakara, Ronald A. Smaldone, Jeremiah J. Gassensmith
Abstract
Metal–organic frameworks (MOFs) have been used to improve vaccine formulations by stabilizing proteins and protecting them against thermal degradation. This has led to increased immunogenicity of these proteinaceous therapeutics. In this work, we show that MOFs can also be used to protect the single-stranded DNA oligomer CpG to increase its immunoadjuvancy. By encapsulation of the phosphodiester CpG in the zinc-based MOF, zeolitic imidazolate framework-8, the DNA oligomer is protected from nuclease degradation and exhibits improved cellular uptake. As a result, we have been able to achieve drastically enhanced B-cell activation in splenocyte cultures comparable to the current state-of-the-art phosphorothioate CpG. Furthermore, we have made a direct comparison of micro- and nanosized MOFs for optimization of the particulate delivery of immunoadjuvants to maximize immune activation.