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Engineered hybrid spider silk particles as delivery system for peptide vaccines

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Lucke Matthias, Mottas Inès, Herbst Tina, Hotz Christian, Römer Lin, Schierling Martina, Herold Heike M., Slotta Ute, Spinetti Thibaud, Scheibel Thomas, Winter Gerhard, Bourquin Carole, Engert Julia,
Project RLR/TLR combination therapy: Mechanisms of T-cell recruitment into gastric tumors
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Original article (peer-reviewed)

Journal Biomaterials
Volume (Issue) 172
Page(s) 105 - 115
Title of proceedings Biomaterials
DOI 10.1016/j.biomaterials.2018.04.008

Abstract

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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