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

Qingliang Kong,Yoshiro Tahara,Masahiro Goto,Momoko Kitaoka,Rie Wakabayashi,Noriho Kamiya

doi:10.3390/pharmaceutics12030240

Qingliang Kong, Yoshiro Tahara + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics12030240

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Journal: Pharmaceutics	Publication Date: Mar 7, 2020
Citations: 1	License type: CC BY 4.0

Affiliation: Kyushu University

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.

Highlights

Japanese cedar (Cryptomeria japonica, JC) pollinosis (JCP) is a type I allergic rhinitis caused by an overreaction to cedar pollen
We summarize the novel antigens that have been tested for Japanese cedar pollinosis (JCP) allergen-specific immunotherapy (AIT), including the use of T cell epitope peptides derived from the JC allergen, modified allergens derived from the JC allergen, DNA vaccines encoding either the JC allergen gene or the T cell epitope peptide gene, and adjuvant conjugations
Based on this present knowledge about AIT, the most important aspect for effective JCP AIT is avoiding side effects associated with antigens and improving the vaccine efficiency of antigens to shorten the duration of the therapy

Summary

Introduction

Japanese cedar (Cryptomeria japonica, JC) pollinosis (JCP) is a type I allergic rhinitis caused by an overreaction to cedar pollen. AIT is the only curative treatment for JCP It involves repeatedly administering the JC allergen to a patient with increasing doses to induce antigen-specific immune tolerance and, reduce the reliance on pharmacotherapy [3,4]. In clinical practice, poor adherence to both the SCIT and SLIT treatment courses has been reported [5] This low compliance may be attributed to the long therapeutic period of up to 3-5 years to achieve the therapeutic effect. The mechanisms of JCP and AIT have been summarized in recent literature [4,10] Based on this present knowledge about AIT, the most important aspect for effective JCP AIT is avoiding side effects associated with antigens and improving the vaccine efficiency of antigens to shorten the duration of the therapy. While most research studies are still at the preclinical stage, the phase I clinical trials of OIT with transgenic rice seeds (UMIN000010212, UMIN000011086, UMIN000016078, UMIN-000024699, UMIN-000024700 and UMIN000034280) have already been completed [11], and OIT with a Cry j 1-galactomannan conjugate (UMIN000011995 and UMIN000013408) and intramuscular immunotherapy with a lysosomal-associated membrane protein (LAMP)-based DNA vaccine (NCT03101267) have been tested in the phase II clinical trials

Cry j Allergens and PE

T Cell Epitope Peptide

DNA Vaccine

Adjuvant Conjugation

Background of Transcutaneous Antigen Delivery

Findings

Conclusions