Synthetic Multicomponent Nanovaccines Based on the Molecular Co-assembly of & beta;-Peptides Protect against Influenza A Virus

Peptideswith the ability to self-assemble into nanoparticles haveemerged as an attractive strategy to design antigen delivery platformsfor subunit vaccines. While toll-like receptor (TLR) agonists arepromising immunostimulants, their use as soluble agents is limitedby their rapid clearance and off-target inflammation. Herein, we harnessedmolecular co-assembly to prepare multicomponent cross-& beta;-sheetpeptide nanofilaments exposing an antigenic epitope derived from theinfluenza A virus and a TLR agonist. The TLR7 agonist imiquimod andthe TLR9 agonist CpG were respectively functionalized on the assembliesby means of an orthogonal pre- or post-assembly conjugation strategy.The nanofilaments were readily uptaken by dendritic cells, and theTLR agonists retained their activity. Multicomponent nanovaccinesinduced a robust epitope-specific immune response and completely protectedimmunized mice from a lethal influenza A virus inoculation. This versatilebottom-up approach is promising for the preparation of synthetic vaccineswith customized magnitude and polarization of the immune responses.