Engineered hybrid spider silk particles as delivery system for peptide vaccines
| Autor: | Martina B. Schierling, Christian Hotz, Thomas Scheibel, Ute Slotta, Heike M. Herold, Julia Engert, Carole Bourquin, Thibaud Spinetti, Tina Herbst, Gerhard Winter, Inès Mottas, Lin Römer, Matthias Lucke |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Ovalbumin Surface Properties Biophysics Silk Priming (immunology) Bioengineering Peptide Biomaterials 03 medical and health sciences Immune system Adjuvants Immunologic Immunity Cytotoxic T cell Animals Humans Spider silk Tissue Distribution Amino Acid Sequence Amino Acids Antigens Particle Size Cell Proliferation chemistry.chemical_classification ddc:615 Drug Carriers ddc:617 biology Macrophages Spiders Dendritic Cells Recombinant Proteins Cell biology Mice Inbred C57BL Drug Liberation 030104 developmental biology chemistry Mechanics of Materials Vaccines Subunit Ceramics and Composites biology.protein Nanoparticles Female Linker T-Lymphocytes Cytotoxic |
| Zdroj: | Biomaterials, Vol. 172 (2018) pp. 105-115 |
| ISSN: | 1878-5905 0142-9612 |
| Popis: | The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable. |
| Databáze: | OpenAIRE |
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