Bacterial Ghosts-Based Vaccine and Drug Delivery Systems

Chen, Haojie; Ji, Hao; Kong, Xiangjun; Lei, Pengyu; Yang, Qinsi; Wu, Wei; Jin, Libo; Sun, Da

doi:10.3390/pharmaceutics13111892

Cited by 51 publications

(38 citation statements)

References 107 publications

(136 reference statements)

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“…The LAGs were purified by separation from live and dead un-evacuated LA cells by subjecting the resuspended bacterial mass to a density gradient centrifugation technique [42] for different time intervals (6,9,12,15, and 18 min) at 168 × g. This was followed by centrifugation of each separated fraction for 20 min at 672 × g to precipitate LAGs. To assess the efficiency of the separation procedure, the purified LAGs obtained at the end of the centrifugation process were examined by light microscopy following toluidine blue staining and TEM imaging.…”

Section: Purificationmentioning

confidence: 99%

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

Saleh

Mahmoud

Eltaher

et al. 2022

Probiotics & Antimicro. Prot.

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Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells, and multiple bioactivities offer promise as drug carriers for colon targeting. Our objective was to evaluate LAGs functionalized with prodigiosin (PG), apoptotic secondary bacterial metabolite, as a bioinspired formulation against colorectal cancer (CRC). LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. LAGs were characterized by microscopic and staining techniques as relatively small-sized uniform vesicles (≈1.6 µm), nearly devoid of cytoplasmic and genetic materials and having a negatively charged intact envelope. PG was highly bound to LAGs envelope, generating a physiologically stable bioactive entity (PG-LAGs), as verified by multiple microscopic techniques and lack of PG release under physiological conditions. PG-LAGs were active against HCT116 CRC cells at both the cellular and molecular levels. Cell viability data highlighted the cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells, anticipating dose reduction for PG and LAGs. Molecularly, expression of the apoptotic caspase 3 and P53 biomarkers in HCT116 intracellular proteins was significantly upregulated while that of the anti-apoptotic Bcl-2 (B-cell lymphoma 2) was downregulated by PG-LAGs relative to PG and 5-fluorouracil. PG-LAGs provide a novel bacteria-based combination for anticancer biomedicine. Graphical abstract

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Section: Purificationmentioning

confidence: 99%

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

Saleh

Mahmoud

Eltaher

et al. 2022

Probiotics & Antimicro. Prot.

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“…Bacterial ghosts are another novel method of vaccine delivery. They are generated from Gram-negative bacteria by inducing release of their intracellular contents, resulting in an empty preserved bacterial envelope with intact surface antigens and PAMPs [ 114 ]. In the first study of its kind, Sheweita et al developed chemically-induced BGs to vaccinate diabetic rats against P. aeruginosa [ 115 ].…”

Section: New Developments In P Aeruginosa Vaccinologymentioning

confidence: 99%

Pseudomonas aeruginosa: Recent Advances in Vaccine Development

2022

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Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound infections, ventilator-associated pneumonia, and chronic infections in people with cystic fibrosis. Antibiotic resistance has rendered many of these infections challenging to treat and novel therapeutic strategies are limited. Multiple clinical studies using well-characterised virulence factors as vaccine antigens over the last 50 years have fallen short, resulting in no effective vaccination being available for clinical use. Nonetheless, progress has been made in preclinical research, namely, in the realms of antigen discovery, adjuvant use, and novel delivery systems. Herein, we briefly review the scope of P. aeruginosa clinical infections and its major important virulence factors.

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“…A currently used method for the generation of BGs is the expression of lysis gene E from synthetic enterobacteria phage KleenX174 (accession number MF426914.1) in Gram-negative bacteria. The protein forms pores in the bacterial membrane, which leads to the subsequent release of cellular contents [ 87 , 88 ]. In this way, BGs from several Gram-negative bacteria have been successfully prepared, including S. Typhimurium [ 89 ], S. enteritides [ 54 ], V. cholerae [ 90 ], H. pylori [ 91 ], H. influenzae [ 92 ], Brucella [ 93 ], and others.…”

Section: Types Of Bacterial Vaccines and The Difficulties Of Vaccinat...mentioning

confidence: 99%

Vaccination against Bacterial Infections: Challenges, Progress, and New Approaches with a Focus on Intracellular Bacteria

Osterloh

2022

Vaccines

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Many bacterial infections are major health problems worldwide, and treatment of many of these infectious diseases is becoming increasingly difficult due to the development of antibiotic resistance, which is a major threat. Prophylactic vaccines against these bacterial pathogens are urgently needed. This is also true for bacterial infections that are still neglected, even though they affect a large part of the world’s population, especially under poor hygienic conditions. One example is typhus, a life-threatening disease also known as “war plague” caused by Rickettsia prowazekii, which could potentially come back in a war situation such as the one in Ukraine. However, vaccination against bacterial infections is a challenge. In general, bacteria are much more complex organisms than viruses and as such are more difficult targets. Unlike comparatively simple viruses, bacteria possess a variety of antigens whose immunogenic potential is often unknown, and it is unclear which antigen can elicit a protective and long-lasting immune response. Several vaccines against extracellular bacteria have been developed in the past and are still used successfully today, e.g., vaccines against tetanus, pertussis, and diphtheria. However, while induction of antibody production is usually sufficient for protection against extracellular bacteria, vaccination against intracellular bacteria is much more difficult because effective defense against these pathogens requires T cell-mediated responses, particularly the activation of cytotoxic CD8+ T cells. These responses are usually not efficiently elicited by immunization with non-living whole cell antigens or subunit vaccines, so that other antigen delivery strategies are required. This review provides an overview of existing antibacterial vaccines and novel approaches to vaccination with a focus on immunization against intracellular bacteria.

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Bacterial Ghosts-Based Vaccine and Drug Delivery Systems

Cited by 51 publications

References 107 publications

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

Pseudomonas aeruginosa: Recent Advances in Vaccine Development

Vaccination against Bacterial Infections: Challenges, Progress, and New Approaches with a Focus on Intracellular Bacteria

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