Engineered hybrid spider silk particles as delivery system for peptide vaccines
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Lucke, Matthias
Department of Pharmacy, Pharmaceutical Technology &
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Mottas, Inès
Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - Ecole de Pharmacie Genève-Lausanne, University of Geneva, Switzerland - Ecolede Pharmacie Genève-Lausanne, Geneva, Switzerland
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Herbst, Tina
Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
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Hotz, Christian
Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
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Römer, Lin
AMSilk GmbH, Planegg/Martinsried, Germany
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Schierling, Martina
University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
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M.Herold, Heike
University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
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Slotta, Ute
AMSilk GmbH, Planegg/Martinsried, Germany
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Spinetti, Thibaud
Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
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Scheibel, Thomas
University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
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Winter, Gerhard
Department of Pharmacy, Pharmaceutical Technology &
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Bourquin, Carole
Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - Ecole de Pharmacie Genève-Lausanne, University of Geneva, Switzerland - Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, Switzerland - Ecolede Pharmacie Genève-Lausanne, Geneva, Switzerland
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Engert, Julia
Department of Pharmacy, Pharmaceutical Technology &
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Published in:
- Biomaterials. - 2018, vol. 172, p. 105–115
English
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.
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Faculty
- Faculté des sciences et de médecine
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Department
- Département de Médecine
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Language
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Classification
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Biological sciences
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License
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License undefined
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Identifiers
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Persistent URL
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https://folia.unifr.ch/unifr/documents/307094
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