Department of Allergy and Rheumatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
Int Arch Allergy Immunol. 2021;182(9):777-787. doi: 10.1159/000512872. Epub 2021 Jul 21.
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.
The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT.
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.
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.
The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.
变应原特异性免疫治疗（AIT）的疗效主要取决于诱导的耐受免疫反应。适当结合的纳米疫苗具有特异性靶向和持续按需释放变应原的优点。
本研究旨在探讨树突状细胞（DCs）靶向纳米疫苗在 AIT 中的作用。
通过将聚乳酸-共-羟基乙酸（PLGA）包封卵清蛋白（OVA）与甘露聚糖结合来制备纳米疫苗。通过流式细胞术、共聚焦显微镜、实时定量 PCR、ELISA 和流式细胞术微珠阵列评估过敏原捕获、人单核细胞来源的 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。
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 hMoDC 捕获，这主要是通过 DC 特异性细胞间黏附分子 3 抓取非整联蛋白介导的。OVA-甘露聚糖-PLGA NP 诱导 hMoDC 呈耐受性表型，但 OVA-PLGA NP 则不然，随后在体外共培养中产生了更多的调节性 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 免疫的 Balb/c 小鼠的血清 OVA 特异性免疫球蛋白水平较低，脾细胞培养中促炎细胞因子的产生较少，而 OVA-甘露聚糖-PLGA 组的脾 Treg 细胞数量高于其他组。此外，用 OVA-甘露聚糖-PLGA NP 进行预免疫显著抑制了 OVA 致敏引起的 Th2 免疫反应。
生物相容性的 PLGA 包封的 OVA 与甘露聚糖结合增强了诱导耐受的能力，可开发为 AIT 的新型疫苗。
