Study on Enhancing Immune Responses Induced by Intranasal Enterovirus 71 Vaccine
Date Issued
2016
Date
2016
Author(s)
Chin, Chiao-Li
Abstract
Mucosal vaccines benefit in convenience of application and pathogen clearance at the site of entry, but are limited in low efficiency to induce immune responses. Administration of an adjuvant could enhance immune responses by building the cytokine environment in favor of mucosal immunity rather than tolerance and promoting mucosal antibody production. To induce these antigen –specific responses, one effective approach is to activate the innate immunity. A range of pathogen associated molecular patterns (PAMP) and damage associated molecular patterns (DAMP) have been postulated to trigger innate immune responses by interacting with pattern recognition receptors (PRR). Of our interest are three innate receptor ligands in the following. Zymosan, a glucan derived from yeasts with β-1, 3-linkage, interacts with Toll-like receptor (TLR) 2/6 heterodimer and dectin-1 on the surface of innate immune cells. Another two include chitosan, a cationic polysaccharide abundant in the cell wall of fungi, and synthetic nanoparticle of silicon dioxide (nano-SiO2). Both of them could activate NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in innate immune cells. In this study, we targeted at the potential immuno-inducibility of zymosan, chitosan and nano-SiO2 as mucosal adjuvants. At the cellular level, we showed that maturation of bone-marrow derived dendritic cells (BMDC) was promoted after treatment with zymosan by inducing IL-10, IL-12 p40 and IL-12 p70 production. Besides, activation of BMDC and bone-marrow derived macrophage (BMDM) were culminated in the induction of IL-1β secretion after sequential treatment with zymosan and chitosan/ nano-SiO2. Based on the in vitro results, we observed that BALB/c mice immunized with antigen plus zymosan exhibited elevated Enterovirus 71 (EV71)- specific immune responses, including the IgG titer in sera, the IgA titer in nasal wash and feces, the proliferation level and IL-17 production from the restimulated splenocytes increased significantly, compared with the antigen alone group. Furthermore, we confirmed minor toxicity of zymosan, chitosan and nano-SiO2 at low concentration both in vitro and in vivo. Taken together, our data suggested that zymosan, chitosan, and nano-SiO2 could be used as potential adjuvants in intranasal EV71 vaccine.
Subjects
Adjuvant
Chitosan
Enterovirus 71
Intranasal vaccine
Nano-SiO2
Zymosan
SDGs
Type
thesis