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Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer.

Shahad K AlsaiariSeba NadeefJohn L DaristotleWilliam T RothwellBujie DuJohnny GarciaLinzixuan ZhangMorteza SarmadiTimothy A ForsterNandita MenonStacey Qiaohui LinLisa H TostanoskiNichole P HachmannErika Yan WangJohn D VenturaDan H BarouchRobert S LangerAna Jaklenec
Published in: Science advances (2024)
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.
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