壳聚糖 - 铝纳米粒子佐剂效应的机理研究

StephenW

Int J Pharm. 2018 Sep 19. pii: S0378-5173(18)30703-8. doi: 10.1016/j.ijpharm.2018.09.044. [Epub ahead of print]
Mechanistic study of the adjuvant effect of chitosan-aluminum nanoparticles.
Lebre F1, de Lima MCP2, Lavelle EC3, Borges O4.
Author information

1
    CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, Universityof Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 PN40, Ireland; Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin 2 D02 PN40, Ireland.
2
    CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
3
    Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 PN40, Ireland; Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin 2 D02 PN40, Ireland.
4
    CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, Universityof Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal. Electronic address: [email protected].

Abstract

The use of tailored particle-based adjuvants constitutes a promising way to enhance antigen-specific humoral and cellular immune responses. However, a thorough understanding of the mechanisms underlying their adjuvanticity is crucial to generate more effective vaccines. We studied the ability of chitosan-aluminum nanoparticles (CH-Al NPs), which combine the immunostimulatory effects of chitosan and aluminum salts, to promote dendritic cell activation, assess their impact on innate and adaptive immune responses and compare the results to those reported for conventional chitosan particles (CH-Na NPs). All tested CH-NP formulations were capable of modulating cytokine secretion by dendritic cells. CH-Al NPs promoted NLRP3 inflammasome activation, enhancing the release of IL-1β without significantly inhibiting Th1 and Th17 cell- polarizing cytokines, IL-12p70 or IL-23, and induced DC maturation, but did not promote pro-inflammatory cytokine production on their own. In vivo results showed that mice injected with CH-Al NPs generated a local inflammatory response comparable to that elicited by the vaccine adjuvant alum. Importantly, after subcutaneous immunization with CH-Al NPs combined with the hepatitis B surface antigen (HBsAg), mice developed antigen-specific IgG titers in serum, nasal and vaginal washes. Overall, our results established CH-Al NPs as a potential adjuvant to enhance both innate and adaptive immune responses.
KEYWORDS:

Adaptive immunity; Adjuvant; Chitosan nanoparticles; Hepatitis B vaccine; Innate immunity

PMID:
    30244149
DOI:
    10.1016/j.ijpharm.2018.09.044

StephenW

Int J Pharm。 2018年9月19日.pii：S0378-5173（18）30703-8。 doi：10.1016 / j.ijpharm.2018.09.044。 [提前打印]
壳聚糖 - 铝纳米粒子佐剂效应的机理研究。
Lebre F1，de Lima MCP2，Lavelle EC3，Borges O4。
作者信息

1
    CNC - 科英布拉大学神经科学与细胞生物学中心，3004-504科英布拉，葡萄牙;科英布拉大学药学院，PólodasCiênciasdaSaúdeAzinhagade Santa Comba，3000-548，Coimbra，Portugal;佐治亚州都柏林圣三一学院生物化学与免疫学院助理研究组2 D02 PN40，Ireland;先进材料生物工程研究中心（AMBER），都柏林三一学院，都柏林2 D02 PN40，爱尔兰。
2
    CNC - 科英布拉大学神经科学与细胞生物学中心，3004-504科英布拉，葡萄牙。
3
    佐治亚州都柏林圣三一学院生物化学与免疫学院助理研究组2 D02 PN40，Ireland;先进材料生物工程研究中心（AMBER），都柏林三一学院，都柏林2 D02 PN40，爱尔兰。
4
    CNC - 科英布拉大学神经科学与细胞生物学中心，3004-504科英布拉，葡萄牙;科英布拉大学药学院，PólodasCiênciasdaSaúdeAzinhagade Santa Comba，3000-548，Coimbra，Portugal。电子地址：[email protected]。

抽象

使用定制的基于颗粒的佐剂构成了增强抗原特异性体液和细胞免疫应答的有希望的方式。然而，彻底了解其辅助机制背后的机制对于产生更有效的疫苗至关重要。我们研究了壳聚糖 - 铝纳米粒子（CH-Al NPs）的能力，它结合了壳聚糖和铝盐的免疫刺激作用，促进树突状细胞活化，评估它们对先天和适应性免疫反应的影响，并将结果与​​报道的结果进行比较。常规的壳聚糖颗粒（CH-Na NPs）。所有测试的CH-NP制剂都能够调节树突细胞分泌细胞因子。 CH-Al NPs促进NLRP3炎性体激活，增强IL-1β的释放而不显着抑制Th1和Th17细胞极化细胞因子，IL-12p70或IL-23，并诱导DC成熟，但不促进促炎细胞因子的产生。他们自己的。体内结果显示注射CH-Al NPs的小鼠产生与疫苗佐剂明矾引起的局部炎症反应相当的局部炎症反应。重要的是，在用CH-Al NPs与乙型肝炎表面抗原（HBsAg）联合皮下免疫后，小鼠在血清，鼻腔和阴道洗液中产生抗原特异性IgG滴度。总体而言，我们的结果确立了CH-Al NPs作为潜在的佐剂，以增强先天性和适应性免疫应答。
关键词：

适应性免疫;辅助;壳聚糖纳米粒;乙型肝炎疫苗;先天免疫

结论：
    30244149
DOI：
    10.1016 / j.ijpharm.2018.09.044