Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization

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...

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Main Authors: Min, Younjin, DeMuth, Peter Charles, Irvine, Darrell J, Hammond, Paula T
Other Authors: Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Format: Article
Language:en_US
Published: Wiley Blackwell 2015
Online Access:http://hdl.handle.net/1721.1/99437
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author Min, Younjin
DeMuth, Peter Charles
Irvine, Darrell J
Hammond, Paula T
author2 Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
author_facet Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Min, Younjin
DeMuth, Peter Charles
Irvine, Darrell J
Hammond, Paula T
author_sort Min, Younjin
collection MIT
description 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.
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spelling mit-1721.1/994372022-09-30T01:17:27Z Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization Min, Younjin DeMuth, Peter Charles Irvine, Darrell J Hammond, Paula T Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Ragon Institute of MGH, MIT and Harvard Koch Institute for Integrative Cancer Research at MIT DeMuth, Peter C. Min, Younjin Irvine, Darrell J. Hammond, Paula T. 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. Ragon Institute of MGH, MIT and Harvard National Institutes of Health (U.S.) (AI095109) United States. Dept. of Defense (Contract W911NF-13-D-0001) United States. Dept. of Defense (Contract W911NF-07-D0004) 2015-10-23T17:28:23Z 2015-10-23T17:28:23Z 2013-07 2013-04 Article http://purl.org/eprint/type/JournalArticle 21922640 http://hdl.handle.net/1721.1/99437 DeMuth, Peter C., Younjin Min, Darrell J. Irvine, and Paula T. Hammond. “Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization.” Advanced Healthcare Materials 3, no. 1 (July 12, 2013): 47–58. en_US http://dx.doi.org/10.1002/adhm.201300139 Advanced Healthcare Materials Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC
spellingShingle Min, Younjin
DeMuth, Peter Charles
Irvine, Darrell J
Hammond, Paula T
Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title_full Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title_fullStr Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title_full_unstemmed Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title_short Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization
title_sort implantable silk composite microneedles for programmable vaccine release kinetics and enhanced immunogenicity in transcutaneous immunization
url http://hdl.handle.net/1721.1/99437
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