Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer
Shahad K. Alsaiari, Seba Nadeef, John L. Daristotle, William T. Rothwell, Bujie Du, Johnny Garcia, Linzixuan Zhang, Morteza Sarmadi, Timothy A. Forster, Nandita Menon, Stacey Qiaohui Lin, Lisa H. Tostanoski, Nicole P. Hachmann, Erika Yan Wang, John D. Ventura, Dan H. Barouch, Róbert Langer, Ana Jaklenec
Abstract
Nanomaterials offer unique opportunities to engineer immunomodulatory activity. In this work, we report the Toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate framework-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal Toll-like receptors, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain trimer, primed rapid humoral and cell-mediated immunity in a dose-sparing manner. Our study offers insights for next-generation adjuvants that can potentially impact future vaccine development.