Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection
Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection
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DOI：
10.1016/j.biomaterials.2015.01.056
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发表时间：
2015-05-01
期刊：
影响因子：
14
通讯作者：
Betbeder, Didier
中科院分区：
文献类型：
--
作者：
Dimier-Poisson, Isabelle;Carpentier, Rodolphe;Betbeder, Didier
亚单位粘膜疫苗的开发需要使用特定的递送系统或免疫调节剂，如佐剂，以提高抗原的免疫原性。纳米粒通过鼻腔途径输送疫苗已引起人们的极大兴趣，但触发有效的粘膜和全身免疫反应的机制仍不清楚。在这里，我们研究了负载弓形虫总抗原(TE)的多孔纳米粒(DGNP)，DGNP将TE输送到呼吸道上皮细胞、巨噬细胞和树突状细胞，以及随后的细胞激活。在体外，DGNP能够稳定、定量地负载复合抗原。DGNP显著的抗原结合量被用来在呼吸道粘膜细胞中传递TE，以诱导细胞成熟，并增加促炎细胞因子的分泌。在急性和慢性弓形虫病小鼠模型上进行了鼻腔疫苗有效性的体内评估。DGNP/TE免疫小鼠后，体内观察到特异性的Th1/Th17应答。这与在存活率和寄生虫负担方面对弓形虫病的高度保护有关，与DGNP在呼吸道粘膜细胞中增加抗原输送有关。这项研究提供了DGNP用于开发针对一系列病原体的新疫苗的潜力的证据。(C)2015爱思唯尔有限公司。保留所有权利。
Development of sub-unit mucosal vaccines requires the use of specific delivery systems or immune-modulators such as adjuvants to improve antigen immunogenicity. Nasal route for vaccine delivery by nanoparticles has attracted much interest but mechanisms triggering effective mucosal and systemic immune response are still poorly understood. Here we study the loading of porous nanoparticles (DGNP) with a total extract of Toxoplasma gondii antigens (TE), the delivery of TE by DGNP into airway epithelial, macrophage and dendritic cells, and the subsequent cellular activation. In vitro, DGNP are able to load complex antigens in a stable and quantitative manner. The outstanding amount of antigen association by DGNP is used to deliver TE in airway mucosa cells to induce a cellular maturation with an increased secretion of pro-inflammatory cytokines. Evaluation of nasal vaccine efficiency is performed in vivo on acute and chronic toxoplasmosis mouse models. A specific Th1/Th17 response is observed in vivo after vaccination with DGNP/TE. This is associated with high protection against toxoplasmosis regarding survival and parasite burden, correlated with an increased delivery of antigens by DGNP in airway mucosa cells. This study provides evidence of the potential of DGNP for the development of new vaccines against a range of pathogens. (C) 2015 Elsevier Ltd. All rights reserved.