Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

Abstract

Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy.

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

“…These data suggest a possible role of the Gantrez ® polymer as Th1-adjuvant in the MN delivery. In fact, the role of SALT in inducing a pro-inflammatory response has been previously shown [36]. Furthermore, high levels of IgA were observed in feces from week 1 after immunization with MNs with 200 µg of the antigenic complex, and protection was achieved against an experimental infection.…”

Skin as an immune organ and clinical applications of skin-based immunotherapy

“…It has been previously observed that epithelial cell status instructs distinct molecular mechanisms, which promote adaptive immune responses [ 13 , 16 ]. Results from a recent study also indicate that the difference in skin depth where the antigen is delivered can induce different immune responses [ 17 ]. When skin is damaged, cutaneous allergen exposure can induce sensitization (Fig.…”

“…While many investigators have shown this important contribution of skin damage to the process of sensitization, others have shown that sensitization occurs even without damage in response to topical exposure [ 17 , 24 , 25 ]. Peanut has been shown to induce sensitization when applied to healthy intact skin through mechanisms mediated by the IL-33 receptor ST2, which result in an altered DC phenotype and a Th2- response, thereby activating the skin’s innate immunity [ 25 ].…”

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

“…Treg) [68,69] or immune activation (e.g. Th1/Th2) [22,70], however, the inflammatory threshold for LC-induced immune activation is yet to be determined. The eMPA defined here induces less skin inflammation than the dMPA, primarily penetrating into the epidermis, resulting in strata-specific APC migration ( Figure 7).…”