Bridging Systemic Immunity with Gastrointestinal Immune Responses via Oil‐in‐Polymer Capsules

Abstract

As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, "immunoticket" capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all-trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut-homing receptors (CCR9). By hitchhiking on the concentration gradient of the CC-motif chemokine ligand 25 (CCL25), the primed DCs would home to the gut associated lymphoid tissues (GALTs) and induce antigen-specific IgA secretion and T cell engagements. Compared with the currently employed RA-involving formulations, the immunoticket capsules stimulate enhanced RA-mediated gut-tropism by mounting the inflammatory innate immunity. Through controlling the RA payload, the potential regulatory T cell engagement is circumvented. In ovalbumin (OVA) and EV71 vaccinations, the immunoticket capsules induce potent serum IgG titer and antigen-specific cytotoxic T cells in the peripheral lymph tissues, as well as robust IgA secretion and T cell engagements on gastrointestinal sites. The data suggest the potential of the immunotickets to serve as a facile, effective, and safe strategy to provide comprehensive immune responses against gastrointestinal infections and diseases.

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

“…This unique delivery system enhanced the expression of the DC surface receptor CCR9 when administered by intramuscular injection. In turn, this resulted in antigen uptake and homing of DCs to the mucosal lymph nodes, successfully inducing mucosal immunity [41].…”

Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

“…Furthermore, the effect was found to be associated with apoptosis-related speck-like proteins (ASC) containing a caspase recruitment domain, and the activation of the MyD88 gene [ 170 ]. More recently, Xia et al coated a core comprising a mixture of squalene and all- trans retinoic acid with a shell of poly(lactic- co -glycolic acid), which was found to enhance the expression of CCR9 on the surface of dendritic cells, resulting in antigen uptake, homing of these cells in the lymph nodes, and, consequently, the induction of strong mucosal immunity [ 171 ].…”

“…A further adjuvant derived from AS01 is AS015, which, combined with CpG oligodeoxynucleotide 7909, has been used in conjunction with a vaccine for melanoma [ 175 , 176 ], and it can also enhance anti-cancer activity [ 177 , 178 ]. Other researchers have used [poly(lactic- co -glycolic acid)] or natural chitosan, which have good safety and biocompatibility profiles, to protect antigens and enhance antigen uptake by APCs [ 171 , 179 ]. Chitosan adjuvants comprise particles of differing forms, sizes, pH values, and surface charges.…”

Research progress of nano-bio-inspired technology

“…Figure 10 Responsive nano-bio-adhesion interface for cell adhesion and release [45] . Cell adhesion/release can be controlled by the chemical reactions of 3D nano-biointerfaces, such as the temperature, endonuclease, light, electricity, and pH (color online) [52] ; B: PLGA微囊"免疫车票" [53] (网络版彩图)…”

“…Figure 11 Immune cell-inspired precision therapy. A: PLGA nanoparticle-stabilized Pickering emulsion vaccine [52] ; B: PLGA immunoticket capsules [53] (color online) 构筑细胞聚集体, 同时还要构建出仿生微血管. 顾忠泽 和赵远锦团队利用微流控技术制备出了三维的细胞聚 集体 [63] , 同样利用微流控技术制备出了可收缩膨胀的 [68] .…”