Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine.
Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine.
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DOI：
10.1007/s11693-010-9066-z
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发表时间：
2011-06-01
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影响因子：
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通讯作者：
Mastrobattista, Enrico
中科院分区：
文献类型：
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作者：
Amidi, Maryam;de Raad, Markus;Mastrobattista, Enrico
脂质体是通用的（亚）微米大小的膜囊泡，可用于多种应用，包括药物递送和体内成像，但它们也代表了人造膜或细胞的优秀模型。几项研究已经证明，体外转录和翻译可以在脂质体内发生，以获得脂质体内功能蛋白的区室化生产（Kita等人，Chembiochem 9（15）：2403-2410，2008; Moritani等人，al.in FEBS J，2010; Kuruma等人，Methods Mol Biol 607：161-171，2010; Murtas等人，Biochem Biophys Res Commun 363（1）：12-17，2007; Sunami等，Anal Biochem 357（1）：128-136，2006;石川等，FEBS Lett 576（3）：387-390，2004; Oberholzer等，Biochem Biophys Res Commun 261（2）：238-241，1999）。这种最小的基于人工细胞的模型对于基于合成生物学的应用是理想的。在这项研究中，我们提出使用脂质体作为人工微生物接种疫苗。这些人工微生物可以通过基因编程随意产生特定的抗原。为了证明这种基于人工细胞的平台的概念，将细菌体外转录和翻译系统以及编码模型抗原β-半乳糖苷酶的基因构建体包埋在多层脂质体内。在小鼠中的疫苗接种研究显示，与对照疫苗（即，没有遗传输入的AnExIL、脂质体β-半乳糖苷酶或编码β-半乳糖苷酶的pDNA）相比，这种抗原表达免疫刺激脂质体（AnExIL）引起针对所产生的抗原（β-半乳糖苷酶）的更高的特异性体液免疫应答。总之，AnExIL为基于DNA的疫苗提供了一个新的平台，该平台将抗原生产、佐剂性和递送结合在一个系统中，并且提供了优于现有疫苗制剂的几个优点。
Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403-2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161-171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12-17, 2007; Sunami et al. in Anal Biochem 357(1):128-136, 2006; Ishikawa et al. in FEBS Lett 576(3):387-390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238-241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen beta-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (beta-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal beta-galactosidase or pDNA encoding beta-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations.