Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy

Abstract

Allergen specific immunotherapy has been shown to be the only effective treatment for long- lasting clinical benefit to IgE-mediated allergic diseases, but a fewer than 5% of patients choose the treatment because of inconvenience and a high risk of anaphylaxis. Recently, epicutaneous allergen-specific immunotherapy (EPIT) has proven effective, yet with limitations owing to strong skin reactions. We demonstrate here safer and faster EPIT, named μEPIT, by delivering powdered allergen and adjuvants into many micropores in the epidermis. We fabricated a microarray patch fractionally coated with a powder mixture of ovalbumin (OVA) model allergen, CpG, and 1,25-dihydroxyvitamin D3 (VD3). Topical application of the patch onto laser- microperforated skin resulted in a high level of epidermal delivery while greatly minimizing allergen leakage into circulation system as compared to current subcutaneous immunotherapy (SCIT). Moreover, only three times of μEPIT over two weeks could sufficiently inhibit allergen- specific IgE responses in mice suffering OVA-induced airway hyperresponsivness (AHR), which was unattainable by eight times of SCIT over three weeks. Mechanistically, μEPIT preferably enhanced IgG2a production suggesting TH1-biased immune responses and induced a high level of T-regulatory (Treg) cells against repeated allergen sensitization. The immune tolerance was confirmed by marked reduction in airway wall thickness as well as eosinophil and neutrophil infiltration into the respiratory airway. The μEPIT represents a novel and painless technology to treat IgE-mediated allergic diseases with little local skin reaction and a minimal risk of anaphylaxis.

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination

“…When inserted into the skin, shafts of the MNA melted away in 10–15 min, exposing the powder to the epidermis (Figure 1D, 2hr). The powder sucked interstitial fluids from the skin tissue, dissolved slowly, and diffused into the epidermis over time against the interstitial fluid influx similarly to the powder drained into laser-generated microchannels previously demonstrated [19,20,28]. The powder was spreading horizontally into the epidermis and then vertically into the upper dermis (Figure 1D).…”

“…This controllable delivery is crucial for BCG vaccine to prevent unwanted infections of other tissues by the bacterium and to ensure the safety of the vaccination. This predominant epidermic delivery is also a key to allergen administration in immunotherapy of allergy to prevent anaphylaxis [20]. In comparison with delivery of powdered vaccines via laser-perforated skin [19,20], the current technology represents a saltation improvement because no laser treatment is required in the current delivery system.…”

“…The powder has to be diluted with saline water and injected within hrs, which often incurs errors owing to inappropriate opening of the glass ampoule and mishandling of the reconstitution. To eliminate the reconstitution procedure and minimize skin irritation, we explored a micro-fractional delivery of powdered vaccines into the skin, in which an array of self-healing microchannels were generated in the epidermis and upper dermis by ablative fractional laser, followed by topical application of powdered vaccine-coated array patches [19,20]. While greatly promoted of powder vaccines into the skin, the laser-perforated skin showed little reactogenicity.…”

Laser adjuvant for vaccination

“…Interestingly, this response was significantly suppressed by co‐application of a TLR agonist CpG‐ODN with the T H 1‐promoting immunomodulatory capacity in these presensitized mice but not by SCIT. Kumar et al similarly treated mice with AFL before application of a model allergen . The group treated the mouse skin with P.L.E.A.S.E.…”

“…Kumar et al similarly treated mice with AFL before application of a model allergen. 80 The group treated the mouse skin with P.L.E.A.S.E. laser to generate 75 micropores per cm 2 (50-75 μm in base diameter and 20-30 μm in depth).…”