Engineering and evaluation of amyloid assemblies as a nanovaccine against the Chikungunya virus

• Published in: Nanoscale 2018-11, Vol.1 (41), p.19547-19556
• Main Authors: Babych, Margaryta, Bertheau-Mailhot, Geneviève, Zottig, Ximena, Dion, Jessica, Gauthier, Laurie, Archambault, Denis, Bourgault, Steve
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amyloidogenic Proteins - chemistry; Anchors; Animals; Antigens; Assemblies; Assembling; Atomic force microscopy; Cell Line; Chikungunya Fever - prevention & control; Chikungunya Fever - veterinary; Chikungunya Fever - virology; Chikungunya virus; Chikungunya virus - metabolism; Circular Dichroism; Coinjection; Density; Dichroism; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; Epitopes - immunology; Fluorescence; Glycoproteins; Immunization; Immunoglobulin G - blood; Macrophages; Macrophages - cytology; Macrophages - immunology; Macrophages - metabolism; Mice; Microscopy; Microscopy, Atomic Force; Nanoparticles; Nanoparticles - chemistry; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Peptides - immunology; Polypeptides; Protein Structure, Secondary; Self-assembly; Solid phase synthesis; Solid phases; Vaccines; Vaccines, Synthetic - immunology; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Viruses
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c8nr05948a

The design of nanoparticles exposing a high density of antigens constitutes a promising strategy to address safety concerns of conventional life-attenuated vaccines as well as to increase the immunogenicity of subunit vaccines. In this study, we developed a fully synthetic nanovaccine based on an amyloid peptide sequence with high self-assembling properties. The immunogenic epitope E2EP3 from the E2 glycoprotein of the Chikungunya virus was used to evaluate the potential of a 10-mer peptide derived from an endogenous amyloidogenic polypeptide as a novel vaccine platform. Chimeric peptides, comprising the peptide antigen attached to the amyloid core by a short flexible linker, were prepared by solid phase synthesis. As observed using atomic force microscopy, these polypeptides self-assembled into linear and unbranched fibrils with a diameter ranging from 6 to 8 nm. A quaternary conformation rich in cross-β-sheets characterized these assemblies, as demonstrated by circular dichroism spectroscopy and thioflavin T fluorescence. ELISA assays and transmission electronic microscopy of immunogold labeled-fibrils revealed a high density of the Chikungunya virus E2 glycoprotein derived epitope exposed on the fibril surface. These amyloid fibrils were cytocompatible and were efficiently uptaken by macrophages. Mice immunization revealed a robust IgG response against the E2EP3 epitope, which was dependent on self-assembly and did not require co-injection of the Alhydrogel adjuvant. These results indicate that cross-β-sheet amyloid assemblies constitute suitable synthetic self-adjuvanted assemblies to anchor antigenic determinants and to increase the immunogenicity of peptide epitopes. A synthetic self-assembled fibrillar nanovaccine decorated with an antigenic determinant from the Chikungunya virus elicits a robust immune response.