Solid-in-Oil Nanodispersions for Transcutaneous Immunotherapy of Japanese Cedar Pollinosis

Abstract

Japanese cedar pollinosis (JCP) is a common affliction caused by an allergic reaction to cedar pollen and is considered a disease of national importance in Japan. Antigen-specific immunotherapy (AIT) is the only available curative treatment for JCP. However, low compliance and persistence have been reported among patients subcutaneously or sublingually administered AIT comprising a conventional antigen derived from a pollen extract. To address these issues, many research studies have focused on developing a safer, simpler, and more effective AIT for JCP. Here, we review the novel antigens that have been developed for JCP AIT, discuss their different administration routes, and present the effects of anti-allergy treatment. Then, we describe a new form of AIT called transcutaneous immunotherapy (TCIT) and its solid-in-oil (S/O) nanodispersion formulation, which is a promising antigen delivery system. Finally, we discuss the applications of S/O nanodispersions for JCP TCIT. In this context, we predict that TCIT delivery by using a S/O nanodispersion loaded with novel antigens may offer an easier, safer, and more effective treatment option for JCP patients.

Keywords: Japanese cedar pollinosis; allergen-specific immunotherapy; solid-in-oil nanodispersions; transcutaneous immunotherapy.

Figure 1

(A) Seven major T cell determinants of Cry j 1 and Cry j 2 in patients with Japanese cedar pollinosis. (B) Amino acid sequence of the hybrid peptide 7Crp. Reproduced from [50] with permission of Elsevier, 2011, and [49], with permission from Elsevier, 2001.

Figure 2

Preparation and application of S/O nanodispersions. Reproduced from [60], which is licensed under a Creative Commons Attribution-(CC BY 4.0) International License.

Figure 3

Requirements for effective transcutaneous immunotherapy of Japanese cedar pollinosis.

Figure 4

(A) Histological analysis of pig skin sections after application of an epitope peptide mixture in PBS solution (PBS sol.) or solid-in-oil nanodispersion (S/O) at 24 and 48 h (SC: stratum corneum; Epi.: epidermis). (B) Serum total IgE and Cry j 1-specific IgE antibody levels after immunotherapy using T cell epitope peptides in pollinosis-model mice. Reproduced from [30] with permission from Elsevier, 2017.

Figure 5

Serum antibody and Th1/Th2 cytokine levels in pollinosis-model mice receiving treatment via TCIT and SCIT. Levels of (A) total IgE, (B) IL-4, (C) IL-10, (D) IL-13, (E) IFN-γ, and (F) IL-12 as measured by ELISA. Reproduced from [35], which is licensed under a Creative Commons Attribution-(CC BY 4.0) International License.