Delivery systems for intradermal vaccination

Abstract

Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development.

Fig. 1

Needles used for ID vaccination. a 32 gauge hypodermic needle with ID bevel used for Mantoux technique injections. b Bifurcated needles used for smallpox vaccination by scarification. c Hollow microneedle developed for reliable ID injection, currently used for ID influenza vaccination (Courtesy of BD). d Mag-11 tattoo needle. e Microneedle injection system, consisting of a single-use syringe coupled to a microneedle shown in part c (Courtesy of BD). f Microneedle injection system containing of a row of four microneedles (Courtesy of NanoPass Technologies)

Fig. 2

Liquid jet and solid projectile injectors. a Jet injector (Biojector 2000) with ID spacer (white portion at end of syringe), used for investigational use only (Courtesy of BioJect). b Jet injector applied to the skin for injection (Courtesy of PharmaJet). c Epidermal powder immunization device for ID projectile injection (Courtesy of PowderMed)

Fig. 3

Solid microneedle patches. a Arrays of solid silicon microneedles coated with gold. (Courtesy of University of Queensland). b Array of solid stainless steel microneedles coated with yellow dye. Each 12 mm by 12 mm device contains 50 microneedles measuring 700 μm tall. Inset shows magnified view of two coated microneedles (Courtesy of Georgia Institute of Technology). c Dissolving microneedles shown intact before insertion into skin, partially dissolved 1 min after insertion into skin and fully dissolved 5 min after insertion into skin (Reproduced from (Sullivan et al. 2010); Courtesy of Georgia Institute of Technology)

Fig. 4

Skin permeabilization methods. a Skin abrasion device, in which a sandpaper device is placed on the skin (1), scraped across the skin in a controlled fashion (2) and then a vaccine patch is applied to the abraded skin (3) (Courtesy of Intecell). b Hand-held skin electroporation device, which uses microneedles as electrodes to cause highly localized electroporation in the skin to facilitate DNA vaccine delivery into skin cells (Courtesy of Cyto Pulse Sciences). c Heat-based device for thermal ablation of the skin. The microheater array (left side of inset) is used to ablate the skin and then a vaccine patch (right side of inset) is applied to the ablated skin (Courtesy of Altea Therapeutics)