Applications of bacterial ghosts in biomedicine.

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.