Zeolitic Imidazolate Frameworks Activate Endosomal Toll-like Receptors and Potentiate Immunogenicity of SARS-CoV-2 Spike Protein Trimer

Nanomaterials offer new opportunities to engineer immunomodulatory activity. In this work, we report the endosomal toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate frameworks-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal TLRs, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a SARS-CoV-2 spike protein receptor binding domain trimer, primed rapid humoral and cell mediated immunity in a dose sparing manner. Our study offers new insights for next-generation adjuvants that can potentially impact future vaccine development.