Comparative study of synthetic nanofilaments assembled from amphiphilic peptides and β-peptides as antigen delivery...

Synthetic peptide vaccines have a high safety profile, although their low immunogenicity requires the use of potent adjuvants and delivery systems. Self-assembling β-peptides and amphiphilic peptides have been identified as versatile building blocks for the preparation of immunostimulating nanocarriers instead of whole protein carrier to display epitopes. However, a direct comparison of the intrinsic immunogenicity of cross-β-sheet nanofilaments and peptide-amphiphile nanofibrils has never been performed. In this study, the amphiphilic peptide C₁₆-V₃A₃K₃ (PA) and the 10-mer self-assembling β-peptide I₁₀ were respectively conjugated with two MHC-peptide epitope models, OVA_253-266 and OVA_323-339, able to polarize the adaptive immune response differently. Synthetic chimeric peptides self-assembled into cytocompatible nanofilaments that induced a robust antigen-specific IgG antibody response in mice, without the need of any additional adjuvants. The profile of IgG subtypes and the cellular immune response offered preliminary indications that PA induced a balanced Th1/Th2 immune response, whereas I₁₀ exhibited a Th1-polarized pro-inflammatory response.