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细菌幽灵平台系统:生产与应用。

The Bacterial Ghost platform system: production and applications.

作者信息

Langemann Timo, Koller Verena Juliana, Muhammad Abbas, Kudela Pavol, Mayr Ulrike Beate, Lubitz Werner

机构信息

BIRD-C GmbH and CoKEG, Kritzendorf, Austria.

出版信息

Bioeng Bugs. 2010 Sep-Oct;1(5):326-36. doi: 10.4161/bbug.1.5.12540.

Abstract

The Bacterial Ghost (BG) platform technology is an innovative system for vaccine, drug or active substance delivery and for technical applications in white biotechnology. BGs are cell envelopes derived from Gram-negative bacteria. BGs are devoid of all cytoplasmic content but have a preserved cellular morphology including all cell surface structures. Using BGs as delivery vehicles for subunit or DNA-vaccines the particle structure and surface properties of BGs are targeting the carrier itself to primary antigen-presenting cells. Furthermore, BGs exhibit intrinsic adjuvant properties and trigger an enhanced humoral and cellular immune response to the target antigen. Multiple antigens of the native BG envelope and recombinant protein or DNA antigens can be combined in a single type of BG. Antigens can be presented on the inner or outer membrane of the BG as well as in the periplasm that is sealed during BG formation. Drugs or supplements can also be loaded to the internal lumen or periplasmic space of the carrier. BGs are produced by batch fermentation with subsequent product recovery and purification via tangential flow filtration. For safety reasons all residual bacterial DNA is inactivated during the BG production process by the use of staphylococcal nuclease A and/or the treatment with β-propiolactone. After purification BGs can be stored long-term at ambient room temperature as lyophilized product. The production cycle from the inoculation of the pre-culture to the purified BG concentrate ready for lyophilization does not take longer than a day and thus meets modern criteria of rapid vaccine production rather than keeping large stocks of vaccines. The broad spectrum of possible applications in combination with the comparably low production costs make the BG platform technology a safe and sophisticated product for the targeted delivery of vaccines and active agents as well as carrier of immobilized enzymes for applications in white biotechnology.

摘要

细菌幽灵(BG)平台技术是一种用于疫苗、药物或活性物质递送以及白色生物技术技术应用的创新系统。BG是源自革兰氏阴性菌的细胞包膜。BG没有所有细胞质内容物,但具有保留的细胞形态,包括所有细胞表面结构。将BG用作亚单位疫苗或DNA疫苗的递送载体时,BG的颗粒结构和表面特性可将载体本身靶向主要抗原呈递细胞。此外,BG具有内在的佐剂特性,可触发对靶抗原增强的体液和细胞免疫反应。天然BG包膜的多种抗原与重组蛋白或DNA抗原可在单一类型的BG中组合。抗原可呈现在BG的内膜或外膜上,也可呈现在BG形成过程中密封的周质中。药物或补充剂也可加载到载体的内腔或周质空间中。BG通过分批发酵生产,随后通过切向流过滤进行产物回收和纯化。出于安全考虑,在BG生产过程中,通过使用葡萄球菌核酸酶A和/或用β-丙内酯处理,使所有残留的细菌DNA失活。纯化后的BG可作为冻干产品在室温下长期储存。从预培养物接种到准备冻干的纯化BG浓缩物的生产周期不超过一天,因此符合快速疫苗生产的现代标准,而不是大量储存疫苗。广泛的可能应用与相对较低的生产成本相结合,使BG平台技术成为一种安全且先进的产品,用于靶向递送疫苗和活性剂以及用于白色生物技术应用的固定化酶载体。

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