| Autor: |
van Strien J; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Makurat M; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Zeng Y; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Olsthoorn R; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Schneider GF; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Slütter B; Department of BioTherapeutics, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., MacKay JA; Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089-9121, United States., Jiskoot W; Department of BioTherapeutics, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Kros A; Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. |
| Abstrakt: |
Subunit vaccines would benefit from a safe particle-based adjuvant. Elastin-like polypeptide (ELP)-based micelles are interesting candidate adjuvants due to their well-defined size and easy modification with protein-based cargo. Coiled coils can facilitate noncovalent modifications, while potentially enhancing antigen delivery through interaction with cell membranes. ELP micelles comprise ELP diblock copolymers that self-assemble above a critical micelle temperature. In this study, an amphiphilic ELP was conjugated to peptide "K", which forms a heterodimeric coiled-coil complex with peptide "E". Self-assembled "covalent" micelles containing ELP-OVA323 (i.e., model antigen OVA323 conjugated to ELP), "coiled-coil" micelles containing ELP-K/E-OVA323 and "hybrid" micelles containing ELP-K and ELP-OVA323 were shown to be monodisperse and spherical. Dendritic cells (DCs) were exposed to all micelle compositions, and T-cell proliferation was investigated. The presence of ELP-K enhanced micelle uptake and subsequent DC maturation, resulting in enhanced CD4 + T-cell proliferation, which makes ELPs with coiled coil-associated antigens a promising vaccine platform. |
