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

Abstract

Subunit vaccines use delivery platforms to present minimal antigenic components 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 solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic components. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid_632-651 and ovalbumin_323-339 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 hemagglutinin_518-526 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.

Keywords: coiled coils; peptide design; self‐assembly; subunit vaccines; synthetic biology.