Preventing allergies by inducing tolerance with an epidermal microprojection patch — ASN Events

Preventing allergies by inducing tolerance with an epidermal microprojection patch (#398)

Nicole van der Burg 1 , Simon Phipps 2 , Pat G Holt 3 , Sandra C I Depelsenaire 1 , Mark A F Kendall 1
  1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
  2. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  3. Telethon Kids Institute, Perth, Western Australia, Australia

Allergic sensitisations affect up to 50% of the population. While guidelines for allergen exposure are improving, few studies [1, 2] have been reported on the active prevention of allergies such as an allergy vaccine. In general, allergies result from a Th2-biased immune response combined with a lack of tolerance to an allergen. Langerhans cells (LC), residing within the epidermis of the skin, promote regulatory T-cells that are essential for allergen tolerance as seen in healthy subjects. Therefore, we have designed and tested a novel skin patch for rapid and precise targeting of allergen to the epidermis, with the aim of inducing allergic tolerance.

Ovalbumin protein was delivered into the epidermis using a custom-designed epidermal microprojection array (eMPA) patch applied for 2 minutes. To test for allergy prevention capabilities, we adapted a tolerance test. This included treating naïve mice repeatedly with an ovalbumin coated eMPA followed by a sensitisation event and airway challenge respectively. Control treatments included intranasal inhalation (10 µg) or intradermal injection (i.d., 1 µg). Tolerance was assessed by eosinophil and mucus influx into the airway and ova-specific IgE and IgG subtyping in sera. Additionally, local skin inflammation at the site of eMPA treatment was assessed by skin histology and enumeration of dead cells.

Relative to i.d., eMPA required 0.1 µg of ovalbumin and half the number treatments to generate a similar tolerance. We hypothesised that this eMPA dose reduction may be due, in part, to the effects of local skin inflammation. Subsequently, we demonstrated that eMPAs induced 14-fold more cell death and 1.2-fold more epidermal swelling at the delivery site than i.d. These findings provide a promising platform as a potential skin-based allergic tolerance approach worthy of further investigation.

  1. [1] Du Toit, G., Roberts, G., Sayre, P.H., Bahnson, H.T, Radulovic, S. et al., Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy. The New England Journal of Medicine, 2016. 375(4): p. 398.
  2. [2] Shakya, A.K., Lee, C.H., and Gill, H.S., Cutaneous vaccination with coated microneedles prevents development of airway allergy. Journal of Controlled Release, 2017. (Accepted manuscript)
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