Evaluation of cylindrical micelles assembled from amphiphilic β-peptides as antigen delivery nanostructures

Abstract

Supramolecular nanostructures assembled from synthetic peptides constitute promising scaffolds for the delivery of antigens for vaccine development. Amphiphilic peptides and self-assembling cross-β-peptides have been shown to promote cellular uptake of antigenic epitopes by antigen-presenting cells, to stimulate the innate immune system and to induce a robust antigen-specific humoral immune response. In this study, we evaluated the use of cylindrical micelles assembled from the amphiphilic β-peptide C16V3A3K3 as a vaccine nanoplatform, combining the properties of cross-β-sheet fibrils and micelles. The ectodomain of the matrix 2 protein (M2e) of the influenza A virus was conjugated with a tetra-Gly linker at the C-terminus of C16V3A3K3. The chimeric peptide assembled into biocompatible unbranched filaments that exposed the antigen on the surface, and these filaments were readily internalized by dendritic cells and activated the toll-like receptor 2/6. These cylindrical micelles induced a robust M2e-specific humoral immune response upon intramuscular immunization in mice without the need for co-administration with adjuvants. Although this strong humoral response did not translate into protection against a lethal infection with the H1N1 influenza virus, these cylindrical micelles assembled from amphiphilic β-peptides expand the repertoire of self-adjuvanted nanostructures to enhance antibody production against peptide epitopes.