Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches.

The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69−84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.

Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen.

INTRODUCTION: There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective. METHODS: Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex. RESULTS: The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment. CONCLUSIONS: Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses. CLINICAL TRIAL REGISTRATION: EudraCT (2013-004726-28).

Micropuncture closure following high density microarray patch application in healthy subjects.

BACKGROUND: The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. MATERIALS AND METHODS: 1 × 1 cm HD-MAP patches containing 5000, 250-µm long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. RESULTS: Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. CONCLUSIONS: Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this paper's demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Innate local response and tissue recovery following application of high density microarray patches to human skin.

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.