title: Implantable silk composite microneedles for programmable vaccine release kinetics and enhanced immunogenicity in transcutaneous immunization.
abstract: Microneedle vaccines mimic several aspects of cutaneous pathogen invasion by targeting antigen to skin-resident dendritic cells and triggering local inflammatory responses in the skin, which are correlated with enhanced immune responses. Here, we tested whether control over vaccine delivery kinetics can enhance immunity through further mimicry of kinetic profiles present during natural acute infections. An approach for the fabrication of silk/poly(acrylic acid) (PAA) composite microneedles composed of a silk tip supported on a PAA base is reported. On brief application of microneedle patches to skin, the PAA bases rapidly dissolved to deliver a protein subunit vaccine bolus, while also implanting persistent silk hydrogel depots into the skin for a low-level sustained cutaneous vaccine release over 1-2 weeks. Use of this platform to deliver a model whole-protein vaccine with optimized release kinetics resulted in >10-fold increases in antigen-specific T-cell and humoral immune responses relative to traditional parenteral needle-based immunization.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, 02139 USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: DeMuth
authors.affiliation: Department of Chemical Engineering, MIT, Cambridge, MA, USA.
authors.forename: Younjin
authors.initials: Y
authors.lastname: Min
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, 02139 USA.|Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.|Institute for Soldier Nanotechnologies, MIT, Cambridge, Massachusetts, 02139 USA.|Department of Materials Science and Engineering, MIT, Cambridge, Massachusetts, 02139 USA.|Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts, 02129 USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland, 20815 USA.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
authors.affiliation: Department of Chemical Engineering, MIT, Cambridge, MA, USA.|Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.|Institute for Soldier Nanotechnologies, MIT, Cambridge, Massachusetts, 02139 USA.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009339:Needles; D047011:Silk / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D047011:Silk; D014612:Vaccines; C006903:carbopol 940
keywords: cutaneous delivery; hydrogels; microneedles; vaccines