Self‐Assembly of Antigenic Peptide Nanofibrils Templates the Growth of Silica Nanoparticles for Nanovaccines

ABSTRACT The low immunogenicity of peptide vaccines remains a critical challenge in immunotherapy. While peptide nanofibrils can function as self‐delivery systems to activate antigen‐presenting cells (APCs), most existing designs rely on complex covalent conjugation to β‐sheet‐forming motifs. Moreover, the diverse surface properties of various antigenic peptides complicate the rational selection of appropriate adjuvants. Herein, we develop a nanovaccine platform in which antigenic peptides self‐assemble into nanofibrils without the need for exogenous β‐sheet‐forming sequences. Silica nanoparticles (SiO ₂ NPs) are nucleated and grown directly along these fibrils, resulting in SiO ₂ @fibril nanovaccines with a unique “beads‐on‐a‐string” morphology. Using amyloid‐β(1‐42) (Aβ42) and human papillomavirus (HPV) type 16 E7 (E7) as model antigens, we demonstrate that these nanovaccines significantly enhance the maturation and activation of bone marrow‐derived dendritic cells (BMDCs). In an Alzheimer's disease animal model using APP/PS1 mice, SiO ₂ @Aβ42 nanovaccines improve motor and cognitive function. Additionally, in an HPV animal model using TC‐1 tumor‐bearing mice, SiO ₂ @E7 nanovaccines suppress tumor growth and increase survival rate. This strategy provides a universal and modular adjuvant platform for peptide‐based nanovaccines.