A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

Subunit vaccines use delivery platforms to present minimal antigenic compo- nents for immunization. The benefits of such systems include multivalency, self-adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self-assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solu- tion. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic com- ponents. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid632-651 and ovalbumin323-339 drive antigen-specific responses both in vitro and in vivo, eliciting both CD4+ T cell and B cell responses. Additionally, SAGEs functionalized with the antigenic peptide hemag- glutinin518-526 from the influenza virus are also able to drive a CD8+ T cell response in vivo. This work demonstrates the potential of SAGEs to act as
a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.