Cutaneous vaccination with coated microneedles prevents development of airway allergy

Abstract

Allergy cases are increasing worldwide. Currently allergies are treated after their appearance in patients. However, now there is effort to make a preventive vaccine against allergies. The rationale is to target patient populations that are already sensitized to allergens but have yet to develop severe forms of the allergic disease, or who are susceptible to allergy development but have not yet developed them. Subcutaneous injections and the sublingual route have been used as the primary mode of preventive vaccine delivery. However, injections are painful, especially considering that they have to be given repeatedly to infants or young children. The sublingual route is hard to use since infants can’t be trained to hold the vaccine under their tongue. In the present study, we demonstrate a microneedle (MN)-based cutaneous preventive allergy treatment against ovalbumin (Ova)-induced airway allergy in mice. Insertion of MNs coated with Ova as a model allergen and CpG oligonucleotide as an adjuvant (MNs-CIT) into the skin significantly induced Ova specific systemic immune response. This response was similar to that induced by hypodermic-needle-based delivery of Ova using the clinically-approved subcutaneous immunotherapy (SCIT) route. MNs-CIT upregulated Ova-specific Th2 cytokines (IL-4, IL-5 & IL-13) and anti-inflammatory cytokines (IL-10) in the bronchoalveolar fluid, and IL-2 and IFN-γ cytokines in restimulated splenocyte cultures. Absence of mucus deposition inside the bronchiole wall and low stiffness around the lung bronchioles after Ova-allergen challenge further confirmed the protective role of MNs-CIT. Overall, MNs-CIT represents a novel minimally invasive cutaneous immunotherapy to prevent the progression of Ova induced airway allergy in mice.

A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

“…As is consistent with MPA application times previously reported in the literature [60,61], the eMPA delivered the desired dose (0.1 µg) of OVA within two minutes. Although coating methods used in this report were crude, leading to a low delivery efficiency (SUPP 1), using a more efficient coating method such as dip coating or inkjet coating would improve dose sparing effects of eMPA delivery to Langerhans cells [62,63].…”

Coated microneedle-based cutaneous immunotherapy prevents Der p 1–induced airway allergy in mice

“…We have previously shown that micron-sized needles widely known as microneedles (MNs) can be used to deliver allergens into the skin. 4 MNs are painless 5 and can bypass the stratum corneum layer to directly deliver the allergen in to the skin. As a result, unlike conventional skin patches, MN-based delivery is not affected by differences in skin permeabilities that naturally exist amongst individuals.…”

Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes

“…the minimum time, it provided confidence that the entire MN cargo was deposited in skin following removal of the device from the tissue. A range of application times (<3 minutes to 1 hour) have been reported for MN coated APIs in murine, guinea pig and rat skin (Cormier et al 2004;Kim et al 2010;Chong et al 2013;Ameri et al 2014;Moreno et al 2017;Shakya et al 2017) and delivery efficiencies vary widely (37->90%). The duration of application required for MN delivery systems is determined, in part, by the solubility of the API and the coating formulation (Zhao et al 2016;Zhao et al 2017), and so poorly soluble macromolecular therapeutics, such as plasmid DNA, may require extended application times (Moreno et al 2017).…”