Implantable silk composite microneedles for programmable vaccine release kinetics and enhanced immunogenicity in transcutaneous immunization

PC DeMuth, Y Min, DJ Irvine… - Advanced healthcare …, 2014 - Wiley Online Library
PC DeMuth, Y Min, DJ Irvine, PT Hammond
Advanced healthcare materials, 2014Wiley Online Library
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 …
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.
Wiley Online Library