Department of Medicinal Chemistry, University of Vienna, Althanstr. 14, UZA2 2B522, 1090, Vienna, Austria.
Adv Exp Med Biol. 2009;655:159-70. doi: 10.1007/978-1-4419-1132-2_12.
Bacterial Ghosts (BG) are empty cell envelopes of Gram-negative bacteria which have been produced by E-mediated lysis. BG are devoid of cytoplasmic content and in combination with the expression of the nuclease SNUC, BG are also devoid of chromosomal and plasmid DNA. Proof of concept and proof of principle studies showed that BG candidate vaccines are highly immunogenic and in many instances induce protective immunity against lethal challenge in animal models. Due to their nature of being bacterial envelope complexes, BG are endowed with intrinsic natural adjuvant activity. BG are able to stimulate the innate and adaptive immune system without any addition of exogenous adjuvants. Although the use of plasmid encoded genetic information is essential for the final make up of BG, BG are not to be considered as genetically manipulated organisms (GMO), as they are nonliving and devoid of genetic information. The latter aspect is of great importance for safety, as no pathogenic islands or antibiotic resistance cassettes can be transferred to other bacteria by horizontal gene transfer. This is an important difference to other chemical-, heat- and pressure- or radiation-inactivated vaccine candidates, which also very often need artificial adjuvants to be added to improve their immunogenicity. The final BG vaccine preparations are freeze dried and are stable for many years at ambient temperature. BG can also be used as carrier and delivery vehicles for drugs or active substances in tumor therapy and due to specific targeting of tumor cells allow a higher specificity of treatment and a reduction of the total amount of drug per application. As carrier of enzymatic activity BG can be used for a new concept of probiotics which can synthesise active compounds from substrates of the environment where they are applied with a certain preference for the gut system. Thus, BG represent a promising technology platform for novel vaccines including combination or DNA vaccines, as drug carriers for therapeutic approaches in tumor treatment and as novel probiotics.
细菌体（BG）是革兰氏阴性菌的空细胞包膜，由 E 介导的裂解产生。BG 不含细胞质内容物，并且与核酸酶 SNUC 的表达相结合，BG 也不含染色体和质粒 DNA。概念验证和原理验证研究表明，BG 候选疫苗具有高度免疫原性，在许多情况下，可在动物模型中诱导针对致死性挑战的保护性免疫。由于其作为细菌包膜复合物的性质，BG 具有内在的天然佐剂活性。BG 能够刺激先天和适应性免疫系统，而无需添加任何外源性佐剂。尽管质粒编码的遗传信息的使用对于 BG 的最终组成至关重要，但 BG 不应被视为遗传修饰生物体（GMO），因为它们是非生命的，并且没有遗传信息。这一方面对于安全性非常重要，因为通过水平基因转移，不会将致病岛或抗生素抗性盒转移到其他细菌中。这与其他化学、热、压力或辐射灭活的疫苗候选物有很大的不同，后者通常需要添加人工佐剂来提高其免疫原性。最终的 BG 疫苗制剂经冷冻干燥，在环境温度下可稳定保存多年。BG 还可以用作药物或活性物质在肿瘤治疗中的载体和递送载体，并且由于对肿瘤细胞的特异性靶向，可以提高治疗的特异性并减少每次应用的药物总量。作为酶活性的载体，BG 可用于一种新的益生菌概念，该概念可以从其应用环境中的底物合成活性化合物，对肠道系统具有一定的偏好。因此，BG 代表了一种有前途的技术平台，可用于新型疫苗，包括组合疫苗或 DNA 疫苗、作为治疗肿瘤的药物载体，以及作为新型益生菌。
