The potential role of using vaccine patches to induce immunity: platform and pathways to innovation and commercialization

Abstract

Introduction: In the last two decades, the evidence related to using vaccine patches with multiple short projections (≤1 mm) to deliver vaccines through the skin increased significantly and demonstrated their potential as an innovative delivery platform.Areas covered: We review the vaccine patch literature published in English as of 1 March 2019, as well as available information from key stakeholders related to vaccine patches as a platform. We identify key research topics related to basic and translational science on skin physical properties and immunobiology, patch development, and vaccine manufacturing.Expert opinion: Currently, vaccine patch developers continue to address some basic science and other platform issues in the context of developing a potential vaccine patch presentation for an existing or new vaccine. Additional clinical data and manufacturing experience could shift the balance toward incentivizing existing vaccine manufactures to further explore the use of vaccine patches to deliver their products. Incentives for innovation of vaccine patches differ for developed and developing countries, which will necessitate different strategies (e.g. public-private partnerships, push, or pull mechanisms) to support the basic and applied research needed to ensure a strong evidence base and to overcome translational barriers for vaccine patches as a delivery platform.

Keywords: Vaccine; human skin; microarray patch; microneedle.

Figure 1:

Vaccine patch development pathway and intensity of efforts (indicated by triangles) required from stakeholders that need to resolve key issues and converge to commercialize a clinical vaccine patch, including successful handoff from patch developers to vaccine manufacturers.

Figure 2:

Process used to identify 116 relevant peer-reviewed vaccine patch papers published in English that met the inclusion criteria.

Figure 3:

Histological preparation of the excised human skin for which the solid horizontal bar represents 100 microns in both panels. Panel A shows a hematoxylin and eosin stained section of paraffin-embedded human skin (original magnification 200x), with capillaries noted by arrows and lymphatics by arrowheads. Panel B shows immunostaining of an adjacent section using antibodies to CD1a with intraepithelial Langerhans Cells noted by arrowheads and CD1a-positive cells in the dermis noted by arrows.

Figure 4

Scale drawing (bar represents 1 mm) with Panel A showing a hematoxylin and eosin stained section of paraffin-embedded human skin showing the relative proportions of keratin, epidermis, papillary dermis, reticular dermis, and subcutaneous adipose tissue, respectively, highlighted in the right-hand side by pseudocolors of red, pink, blue, no color, and yellow, respectively. Panel B shows an image from high frequency ultrasound (40 MHz) (adapted with permission from [145]), Panel C shows detail in the dermis and superficial subcutaneous tissue by ultrasound imaging at ultrahigh frequencies (70 MHz shown) (adapted with permission under Creative Common license http://creativecommons.org/licenses/by/4.0/ from supplementary data in [167]). Panel D shows simultaneous dual-band line-field confocal optical coherence tomography (OCT) (adapted with permission from [168] © The Optical Society) that provides very high resolution (note the significant cellular detail in the inset below at the level of the epidermis and superficial papillary dermis not visible in Panels B and C), which comes at the expense of relatively short penetration depth. Panel E shows a single dissolving projection (adapted with permission from [64]) on the left, and a single coated nanopatch projection (adapted with permission under Creative Common license http://creativecommons.org/licenses/by/4.0/ from [92]). Finally, the black rectangle drawn at the base of the needle corresponds to the position of the corresponding vaccine patch inner surface.