(720d) Controlling the Skin’s Delicate Immune Balance – from Microneedle Immunotherapy to Allergy Model Development

The skin is the largest organ in the body and provides a formidable first line of defense against the ingress of pathogens and other foreign agents. Much of the skin’s barrier property is provided by the stratum corneum (SC) – a highly keratinized, tortuous outermost layer about 10-20 µm thick. Beneath the SC lies the viable epidermis with its vast network of immunocompetent cells – such as the Langerhans and dendritic cells. These cells locally monitor the skin for damage and ingress of foreign material, and promptly evoke systemic immune responses. These triggered immune responses are not generic but highly influenced by factors such as the extent of skin damage and the inherent nature of the foreign agent(s). Similarly, when administering therapeutic agents into the skin, ‘gentle’ delivery approaches are received with favor by the immune system, whereas harsh delivery methods can incite inflammation and a hostile immune response.

In this talk, immunocompetence of the skin will be discussed with focus on tailoring immune responses in-vivo in rodents and miniature swine for two different applications: (i) allergen immunotherapy (AIT) using coated microneedles (ii) peanut and milk allergy disease models that will enable evaluation of newly developing immunotherapies. The first part of the talk will describe the use of coated microneedle (MN) patches for allergen immunotherapy. The MN patches comprised 57 individual needles, each measuring 700 µm in length. We demonstrate (a) the coating of these MN patches with a variety of biologics (b) reproducible delivery of the coated biologics in mice and pigs, and (c) the ability of these coated MN patches in evoking allergen-specific antibody responses in both blood and mucosa in a ‘benevolent’ manner that will be conducive to the desensitization of allergic subjects to different foods. We also compare MN-mediated delivery with other conventional methods – comparing safety and efficacy.

The second phase of the talk will describe how administering molecules into the skin in a less ‘gentle’ manner causes allergies rather than producing a therapeutic effect. We will discuss the development of milk and peanut allergies in mice and pigs respectively. For this application, we damage the skin in controlled amounts by tape-stripping to disrupt the SC barrier. The damaged skin is then exposed to an allergen of interest (milk/peanut proteins) to achieve ‘hostile’ allergic sensitization. We have developed multiple allergy models with 100% success rates by controlled exposure of allergen to damaged skin alone or in combination with oral and intraperitoneal exposure. Subsequently, we characterized the degree of allergic manifestation via evaluation of clinical symptoms of allergic reactions such as vomiting and cutaneous anaphylaxis upon oral/intraperitoneal food challenges, survival rate, and analysis of various serological markers.

Overall, this talk should provide a starting point, and guidelines for manipulating the skin microenvironment to achieve highly tailored immune responses for developing allergic disease models and novel immunotherapies.