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

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.

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

“…T cell epitope peptide Epitope p246-259 of Cry j 2 Oral Suppression of Th1 and Th2 responses [20,21] Integrated peptide from three epitopes Oral Inhibition of lymph node cell proliferation to epitopes from Cry j 1/2 [22] Rice seed containing peptides from fourteen epitopes Oral - [23] Rice seed containing 7Crp from seven epitopes Oral Inhibition of T-cell proliferative response to Cry j 1 [24] Chicken egg containing 7Crp from seven epitopes Oral Induction of oral tolerance [25] Cry-consensus from five or six epitopes SC Induction of IgG2a, suppression of ratios of IL-4/IFN-γ and IL-5/IFN-γ,Th1 deviation [17,26] 7Crp from seven epitopes SL Induction of IL-10-producing regulatory T cells [27] 7CrpR from seven epitopes T - [28] Mixture of seven epitopes T Suppression of Th1 and Th2 responses [29] [46] 7CrpR from seven epitopes combined with R848 T Induction of IgG 2a/IgE ratio, Th1 deviation [47] ID: intradermal, IM: intramuscular, SC: subcutaneous, SL: sublingual, T: transcutaneous.…”

Application of built-in adjuvants for epitope-based vaccines

“…Therefore, a built-in adjuvant exhibiting both the functions of a transmission system and a traditional adjuvant, is constructed within the vaccine to improve the immunogenicity of epitope peptides by stimulating the innate immune response required for an adaptive immune response. To achieve this goal, the epitopes are regularly fused with adjuvant proteins (e.g., toll-like receptor (TLR) ligands and proteins that can spontaneously assemble into virus-like particles (VLPs)) or displayed on the surface of some particular biomaterials (e.g., liposomes, gold nanoparticles, and poly(lactic- co -glycolic acid) (PLGA)) and the immunogenicity of the epitopes are significantly increased by this immune complex (Chen et al, 2017; Rueda et al, 2017; Kitaoka et al, 2017; Karuturi et al, 2017). This review primarily introduces the methods for applying built-in adjuvants in the design of epitope-based vaccines, including a few new delivery systems (e.g., dendrimers, self-assembled peptide nanoparticles (SAPNs), and hyperbranched polyglycerol (hbPG)) (Busseron et al, 2013; Glaffig et al, 2015; Indelicato, Burkhard & Twarock, 2017).…”

Editorial: The launch phase of Bioengineering & Translational Medicine

“…In terms of scientific topics, BioTM has focused on subjects where Engineering, Chemical Engineering in particular, has made a strong fundamental and translational impact on the field. These topics include drug delivery, Nucleic acid delivery, Regenerative Medicine, Biotechnology, Nanomedicine, Biomedical Devices, and immunotherapy . We look forward to continue building our strengths in these fields and expand the list to include additional key areas.…”