Engineered hybrid spider silk particles as delivery system for peptide vaccines

Lucke, Matthias; Mottas, Inès; Herbst, Tina; Hotz, Christian; Römer, Lin; Schierling, Martina; M.Herold, Heike; Slotta, Ute; Spinetti, Thibaud; Scheibel, Thomas; Winter, Gerhard; Bourquin, Carole; Engert, Julia

doi:10.1016/j.biomaterials.2018.04.008

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Journal article

Engineered hybrid spider silk particles as delivery system for peptide vaccines

Lucke, Matthias Department of Pharmacy, Pharmaceutical Technology &amp
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
Herbst, Tina Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Hotz, Christian Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Römer, Lin AMSilk GmbH, Planegg/Martinsried, Germany
Schierling, Martina University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
M.Herold, Heike University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
Slotta, Ute AMSilk GmbH, Planegg/Martinsried, Germany
Spinetti, Thibaud Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Scheibel, Thomas University of Bayreuth, Faculty of Engineering Science, Chair for Biomaterials, Bayreuth, Germany
Winter, Gerhard Department of Pharmacy, Pharmaceutical Technology &amp
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
Engert, Julia Department of Pharmacy, Pharmaceutical Technology &amp

01.07.2018

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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language