Background: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. Objectives: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. Methods: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. Results: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. Conclusions: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.
Int Arch Allergy Immunol

中文翻译：

---

通过将聚乳酸-Co-乙醇酸包封的过敏原与甘露聚糖偶联的树突状细胞靶向纳米疫苗诱导调节性 T 细胞

背景：过敏原特异性免疫疗法 (AIT) 的疗效主要取决于引发的致耐受性免疫反应。正确结合的纳米疫苗具有特异性靶向和持续按需释放过敏原的优点。目的：本研究的目的是研究靶向树突细胞 (DC) 的纳米疫苗对 AIT 的影响。方法：纳米疫苗是通过将聚乳酸-乙醇酸共聚物 (PLGA) 包裹的卵清蛋白 (OVA) 与甘露聚糖偶联而成的。通过流式细胞术、共聚焦显微镜、定量实时 PCR、ELISA 和细胞计数珠阵列评估过敏原捕获、人类单核细胞衍生的 DC (hMoDC) 激活和 T 细胞反应。用纳米疫苗免疫 Balb/c 小鼠，并分析免疫反应。结果：OVA-PLGA 纳米颗粒 (NP) 显示出良好的安全性。OVA-甘露聚糖-PLGA NP 比 OVA-PLGA NP 更有效地被 hMoDCs 捕获，这主要是通过 DC 特异性细胞间粘附分子 3-抓取非整合素介导的。hMoDCs 的致耐受表型由 OVA-甘露聚糖-PLGA NP 诱导，但不是 OVA-PLGA NP，并且随后在体外共培养中产生了数量增加的调节性 T (Treg) 细胞。与用 OVA-PLAG NP、PLGA NP 或 OVA 免疫的小鼠相比，用 OVA-甘露聚糖-PLGA NP 免疫 Balb/c 小鼠导致较低的血清 OVA 特异性免疫球蛋白水平和脾细胞培养物中促炎细胞因子的产生较少，而OVA-甘露聚糖-PLGA组脾脏Treg细胞数量高于其他组。而且，结论：与甘露聚糖偶联的生物相容性 PLGA 封装的 OVA 具有增强的耐受诱导能力，可以开发为 AIT 的新型疫苗。
Int Arch 过敏免疫