Local Response to Microneedle-Based Influenza Immunization in the Skin

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Microneedle patches (MN) provide a novel method of vaccine delivery to the skin with the objective of targeting the large network of resident antigen-presenting cells to induce an efficient immune response. Our previous reports demonstrated that cutaneous delivery of inactivated influenza virus-coated MN to mice protects against lethal infection. Protection is correlated with sustained levels of anti-influenza virus serum antibodies, hemagglutination inhibition titers, and robust cellular responses that are often stronger than those generated by intramuscular vaccination. Here we dissect the early events occurring in murine skin after microneedle delivery of inactivated influenza virus. We demonstrate correlation of immunization against influenza virus with a local increase of cytokines important for recruitment of neutrophils, monocytes and dendritic cells at the site of immunization. We also observed prolonged antigen deposition, and migration of matured dendritic cells bearing influenza virus antigen from the skin.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>The immunological mechanisms by which MN vaccination confers protective immunity are not well understood. The present study provides a first analysis of the early immune events after microneedle-based vaccination.</jats:p>

Langerin negative dendritic cells promote potent CD8 + T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

“…T-cell priming by microfabricated vaccine delivery platforms is attributed to Ag capture and/or presentation by LCs (6,(8)(9)(10). Indeed, our confocal imaging revealed fluorescent MA cargo distributed within the epidermis and dermis, hence potentially accessible to epidermal resident LCs, and LCs either trafficking through the dermis (27) in vivo cross-presentation of Candida albicans-derived Ag has been reported (13).…”

“…Designs under evaluation have largely been restricted to nonlive vaccine platforms (6,(8)(9)(10). However, for HIV, induction of high frequency protective CD8…”

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

“…However, migration of cells can occur, initiated by the release of molecules, such as cytokines and chemokines, from skin cells (Ueno et al 2007;Koutsonanos et al 2013). These molecules provide a signal to cells from both inside and outside the skin to migrate towards the location of secretion (Del Pilar Martin et al 2012;Koutsonanos et al 2013) and thereby repopulating the skin and changing the number and distribution of cells within the skin. In addition, these signaling molecules can influence the maturation and migration of antigen presenting cells towards the lymph nodes (Koutsonanos et al 2013).…”

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

“…However, microneedles are known to elicit local skin reactions, such as transient erythema and increased blood flow [28], indicative of momentary changes in skin protein profile. For example, local expression of some cytokines, including IL-1β and TNF-α, was elevated 6 hours after microneedle administration [29]. It is not clear whether significant microneedle-induced local protein expression would occur within the much shorter time frame (≤1 hour) required for our antigen extraction and the extent of any such interference with antigen detection.…”