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 com- ponents. 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.

The de novo design of α-helical peptides for supramolecular self-assembly

“…When added to epithelial cells, SAGE particles show no cytotoxicity and are endocytosed at rates that can be controlled by varying surface electrostatics [36]. Furthermore, antigenic peptides can be extended from the homotrimer component to drive selective and assembly-dependent immune responses in vitro and in vivo [37]. Thus, the SAGE system is highly modular, comprises fully de novo peptides assembling into a unique non-natural architecture and shows promise for cell-biology and biomedical applications.…”

IUPAC‐Zhejiang‐NHU‐Preise Max‐Planck‐Bristol‐Kooperation: Zentrum für minimale Biologie

“…Schwille und Weil sind Kuratoriumsmitglieder der Angewandten Chemie , und Mann gehörte von 2000 bis 2009 ihrem internationalen Beirat an. Mitglieder des neuen Zentrums berichteten kürzlich in der Angewandten Chemie über tanzende Vesikel, synthetische Protozellen und DNAzym‐Polymer‐Nanostrukturen und in Advanced Functional Materials über synthetische Vakzin‐Plattformen und programmierbare Tröpfchengrenzflächen . Das gemeinsame Projekt von University of Bristol und Max‐Planck‐Gesellschaft beginnt im August 2019 und hat eine Mindestlaufzeit von fünf Jahren.…”

IUPAC–Zhejiang NHU Awards Max Planck–Bristol Centre for Minimal Biology

“…Schwille and Weil are current members of the Editorial Board of Angewandte Chemie and Mann was a member of the International Advisory Board (2000–2009). Members of the Centre have recently published in Angewandte Chemie on beating vesicles, synthetic protocells, and DNAzyme–polymer nanostructures, and in Advanced Functional Materials on synthetic vaccine platforms and programmable droplet interfaces . The partnership between the University of Bristol and the Max Planck Society will begin in August 2019 and extend for at least five years.…”