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 2018-07-01 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. application/pdf https://folia.unifr.ch/global/documents/307094 https://folia.unifr.ch/documents/307094/files/mot_ehs.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biomaterials.2018.04.008 info:eu-repo/semantics/openAccess License undefined Biomaterials. - 2018, vol. 172, p. 105–115 info:eu-repo/classification/udc/57 Engineered hybrid spider silk particles as delivery system for peptide vaccines http://purl.org/coar/resource_type/c_6501