Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis
Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis
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DOI：
10.1016/j.vaccine.2011.07.039
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发表时间：
2011-09-16
期刊：
影响因子：
5.5
通讯作者：
Swartz, Melody A.
中科院分区：
文献类型：
--
作者：
Ballester, Marie;Nembrini, Chiara;Swartz, Melody A.
为了预防和治疗目的，需要驱动针对结核分枝杆菌（Mtb）的强大T细胞免疫的疫苗。我们最近开发了一种具有Pluronic稳定的聚硫化丙烯纳米颗粒（NP）的合成疫苗递送平台，其通过其小尺寸（类似于30 nm）靶向淋巴组织，并通过其表面化学激活补体级联。在这里，我们将结核抗原Ag 85 B与NP（NP-Ag 85 B）缀合，并比较它们在皮内或肺部施用后在小鼠中引发相关免疫应答的功效。与含CpG的可溶性Ag 85 B和皮内递送制剂相比，含佐剂CpG的NP-Ag 85 B的肺部给药导致脾、肺和肺引流淋巴结中抗原特异性多功能Th 1应答的诱导增强。用这种含佐剂的NP制剂和疫苗接种途径也观察到粘液和全身性Th 17应答，特别是在肺中。然后，我们评估了在Mtb气溶胶攻击后由含佐剂的NP制剂诱导的保护，并发现与含CpG的可溶性Ag 85 B和相应的皮内递送制剂相比，通过肺部途径用NP-Ag 85 B和CpG接种显示肺细菌负荷的显著降低。这些发现强调了通过肺途径施用基于NP的制剂用于TB疫苗接种的潜力。(C)2011爱思唯尔有限公司保留所有权利。
Vaccines that drive robust T-cell immunity against Mycobacterium tuberculosis (Mtb) are needed both for prophylactic and therapeutic purposes. We have recently developed a synthetic vaccine delivery platform with Pluronic-stabilized polypropylene sulfide nanoparticles (NPs), which target lymphoid tissues by their small size (similar to 30 nm) and which activate the complement cascade by their surface chemistry. Here we conjugated the tuberculosis antigen Ag85B to the NPs (NP-Ag85B) and compared their efficacy in eliciting relevant immune responses in mice after intradermal or pulmonary administration. Pulmonary administration of NP-Ag85B with the adjuvant CpG led to enhanced induction of antigen-specific polyfunctional Th1 responses in the spleen, the lung and lung-draining lymph nodes as compared to soluble Ag85B with CpG and to the intradermally-delivered formulations. Mucosal and systemic Th17 responses were also observed with this adjuvanted NP formulation and vaccination route, especially in the lung. We then evaluated protection induced by the adjuvanted NP formulation following a Mtb aerosol challenge and found that vaccination with NP-Ag85B and CpG via the pulmonary route displayed a substantial reduction of the lung bacterial burden, both compared to soluble Ag85B with CpG and to the corresponding intradermally delivered formulations. These findings highlight the potential of administrating NP-based formulations by the pulmonary route for TB vaccination. (C) 2011 Elsevier Ltd. All rights reserved.