http://jpharmsci.org/article/S0022354922000326/pdf

Uptake Kinetics of Liposomal Formulations of Differing Charge Influences Development of In Vivo Dendritic Cell Immunotherapy.

Skin as an immune organ and the site of biomimetic, non-invasive vaccination

Self-amplifying RNA vaccine protects mice against lethal Ebola virus infection.

Summary Allergen immunotherapy (AIT) is the only disease-modifying therapy for allergic disease. Through repeated inoculations of low doses of allergen—either as whole proteins or peptides—patients can achieve a homeostatic balance between inflammatory effectors induced and/or associated with allergen contact, and mediators of immunologic non-responsiveness, potentially leading to sustained clinical improvements. AIT for airborne/respiratory tract allergens and insect venoms have traditionally been supplied subcutaneously, but other routes and modalities of administration can also be effective. Despite differences of allergen administration, there are some similarities of immunologic responses across platforms, with a general theme involving the restructuring and polarization of adaptive and innate immune effector cells. Here we review the immunology of AIT across various delivery platforms, including subcutaneous, sublingual, epicutaneous, intradermal, and intralymphatic approaches, emphasizing shared mechanisms associated with achieving immunologic non-responsiveness to allergen.

Immunology of allergen immunotherapy

The skin is an attractive alternative administration route for allergy vaccination, as the skin is rich in dendritic cells (DCs) and is easily accessible. In the skin multiple subsets of DCs with distinct roles reside at different depths. In this study antigen (= allergen for allergy) formulations were injected in ex vivo human skin in a depth-controlled manner by using a hollow microneedle injection system. Biopsies were harvested at the injection site, which were then cultured for 72 hours. Subsequently, the crawled-out cells were collected from the medium and analyzed with flow cytometry. Intradermal administration of ovalbumin (OVA, model antigen) solution at various depths in the skin did not affect the migration and maturation of DCs. OVA was taken up efficiently by the DCs, and this was not affected by the injection depth. In contrast, Bet v 1, the major allergen in birch pollen allergy, was barely taken up by dermal DCs (dDCs). Antigens were more efficiently taken up by CD14+ dDCs than CD1a+ dDCs, which in turn were more efficient at taken up antigen than Langerhans cells. Subsequently, both OVA and Bet v 1 were formulated in cationic and anionic liposomes, which altered antigen uptake drastically following intradermal microinjection. While OVA uptake was reduced by formulation in liposomes, Bet v 1 uptake in dDCs was increased by encapsulation in both cationic and anionic liposomes. This highlights the potential use of liposomes as adjuvant in intradermal allergy vaccine delivery.

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L. Kong

Papers

Antigen uptake after intradermal microinjection depends on antigen nature and formulation, but not on injection depth