title: Controlled release of a model vaccine by nanoporous ceramic microneedle arrays.
abstract: Current vaccination technology can advance from the use of novel ceramic nanoporous microneedle arrays (npMNA), where the material serves as a storage reservoir for vaccines. Moreover, npMNA will enhance vaccine efficacy by more precisely reaching skin dendritic cells, the kickstarters of T and B cell immunity. In the present study we assessed the efficacy of vaccination using npMNAs by in vivo application of OVA257-264 peptides mixed with agonistic anti-CD40 antibodies as adjuvant. The induction of OVA-specific CD8(+) T cells via npMNA was comparable with the frequency induced via intradermal injection using needle-syringe. However, only when expanding the vaccination area by using two npMNAs the frequencies of induced IFN-γ-specific effector CD8(+) T cells were comparable with those induced via needle-syringe injection. Analysis of vaccine release from npMNA in a human ex vivo skin explant model revealed that OVA257-264 peptides were indeed delivered intradermal, and release also increased by prolonging the npMNA application time on the human skin. Together, our studies demonstrate the potential of npMNA for vaccine delivery in human skin and in vivo induction of CD8(+) effector T cell responses.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; MyLife Technologies B.V., The Netherlands.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Boks
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: Unger
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Steef
authors.initials: S
authors.lastname: Engels
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; MyLife Technologies B.V., The Netherlands.
authors.forename: Martino
authors.initials: M
authors.lastname: Ambrosini
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvette van
authors.initials: Yv
authors.lastname: Kooyk
authors.affiliation: Department of Mechanical Engineering, Microsystems group and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, The Netherlands; MESA+ Institute for Nanotechnology, University of Twente, The Netherlands; MyLife Technologies B.V., The Netherlands. Electronic address: r.luttge@tue.nl.
authors.forename: Regina
authors.initials: R
authors.lastname: Luttge
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002516:Ceramics / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006801:Humans; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D008810:Mice, Inbred C57BL; D036103:Nanotechnology; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012867:Skin; D019864:Somatostatin-Secreting Cells / Q000276:immunology; D013594:Syringes; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D019013:CD40 Antigens; D003692:Delayed-Action Preparations; C110366:OVA-8; D010446:Peptide Fragments; D014612:Vaccines; D010047:Ovalbumin
keywords: (Anti-tumor) CD8(+) T cell response; (Trans)dermal drug delivery; Ceramic nanoporous microneedles; Human skin; Vaccine delivery