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      Transcutaneous pollinosis immunotherapy using a solid‐in‐oil nanodispersion system carrying T cell epitope peptide and R848

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          Abstract

          Antigen‐specific immunotherapy is the only curative approach for the treatment of allergic diseases such as Japanese cedar pollinosis. Immunotherapy using a T cell epitope vaccine in combination with the adjuvant R848 is of particular interest as a safe and effective approach to treat allergic diseases. Herein, we propose a simple and easy to handle vaccine administration method using the original solid‐in‐oil (S/O) nanodispersion system that permeates through the skin. The S/O nanodispersion system is composed of nanoparticles of hydrophilic molecules surrounded with hydrophobic surfactants that are dispersed in an oil vehicle. The system has potential to carry and deliver both hydrophilic and hydrophobic bioactives. Hydrophilic T cell epitope peptide was efficiently delivered through mouse skin using the S/O nanodispersion system and lowered antigen‐specific IgE levels in pollinosis model mice. Addition of the hydrophobic adju1vant R848 significantly lowered the antibody secretion and shifted the Th1/Th2‐balance toward Th1‐type immunity in the model mice, showing the potential to alleviate Japanese cedar pollinosis.

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          Peptide Vaccine: Progress and Challenges

          Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.
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            The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells.

            The skin is a highly complex organ interspersed with a variety of smaller organ-like structures and a plethora of cell types that together perform essential functions such as physical sensing, temperature control, barrier maintenance and immunity. In this Review, we outline many of the innate and adaptive immune cell types associated with the skin, focusing on the steady state in mice and men, and include a broad update of dendritic cell function and T cell surveillance.
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              Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens

              Substantial progress in understanding mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumors, organ transplantation and chronic infections has led to a variety of targeted therapeutic approaches. Allergen-specific immunotherapy (AIT) has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific way of treatment. The mechanisms by which allergen-AIT has its mechanisms of action include the very early desensitization effects, modulation of T- and B-cell responses and related antibody isotypes as well as inhibition of migration of eosinophils, basophils and mast cells to tissues and release of their mediators. Regulatory T cells (Treg) have been identified as key regulators of immunological processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in AIT. Naturally occurring FoxP3+ CD4+CD25+ Treg cells and inducible type 1 Treg (Tr1) cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector Th1, Th2 and Th17 cells; suppression of allergen-specific IgE, and induction of IgG4; suppression of mast cells, basophils and eosinophils and suppression of effector T cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and regulatory T cell subsets.
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                Author and article information

                Contributors
                m-goto@mail.cstm.kyushu-u.ac.jp
                Journal
                Bioeng Transl Med
                Bioeng Transl Med
                10.1002/(ISSN)2380-6761
                BTM2
                Bioengineering & Translational Medicine
                John Wiley and Sons Inc. (Hoboken )
                2380-6761
                03 February 2017
                March 2017
                : 2
                : 1 ( doiID: 10.1002/btm2.v2.1 )
                : 102-108
                Affiliations
                [ 1 ] Dept. of Applied Chemistry Kyushu University 744 Moto‐oka Fukuoka 819‐0395 Japan
                [ 2 ] Dept. of Chemical Engineering Kyushu University 744 Moto‐oka Fukuoka 819‐0395 Japan
                [ 3 ] Advanced Transdermal Drug Delivery Center Kyushu University 744 Moto‐oka Fukuoka 819‐0395 Japan
                [ 4 ] Center for Future Chemistry Kyushu University 744 Moto‐oka Fukuoka 819‐0395 Japan
                Author notes
                [*] [* ] Correspondence Masahiro Goto, Graduate School of Engineering, Kyushu University, 744 Moto‐oka, 819‐0395 Fukuoka, Japan. Email: m-goto@ 123456mail.cstm.kyushu-u.ac.jp .
                Article
                BTM210048
                10.1002/btm2.10048
                5689524
                01eaa3e8-3c62-4e08-ac28-f3025a5881f0
                © 2017 The Authors. Bioengineering & Translational Medicine is published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 August 2016
                : 17 November 2016
                : 19 November 2016
                Page count
                Figures: 5, Tables: 0, Pages: 7, Words: 5249
                Funding
                Funded by: Grant‐in‐Aid for Scientific Research (S)
                Award ID: 16H06369
                Funded by: Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Categories
                Research Report
                Research Reports
                Custom metadata
                2.0
                btm210048
                March 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.5 mode:remove_FC converted:16.11.2017

                immunotherapy,r848,resiquimod,solid‐in‐oil nanodispersion,t cell epitope,transcutaneous drug delivery

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