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

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 (SiO2 NPs) are nucleated and grown directly along these fibrils, resulting in SiO2@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, SiO2@Aβ42 nanovaccines improve motor and cognitive function. Additionally, in an HPV animal model using TC-1 tumor-bearing mice, SiO2@E7 nanovaccines suppress tumor growth and increase survival rate. This strategy provides a universal and modular adjuvant platform for peptide-based nanovaccines.