Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

Lin, Ivan Y. C.; Van, Thi Thu Hao; Smooker, Peter M.

doi:10.3390/vaccines3040940

Cited by 93 publications

(88 citation statements)

References 190 publications

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“…The use of food grade LAB for oral DNA vaccines is a safer alternative than the use of attenuated pathogenic bacteria, such as Shigella , Salmonella , Yersinia , and Listeria for DNA-delivering into mammalian cells 42, 43. To this end, we have reported the construction of a new shuttle vector called pExu for DNA delivery to be used in food grade bacteria, like L. lactis .…”

Section: Discussionmentioning

confidence: 99%

A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays

Mancha-Agresti

Drumond

Carmo

et al. 2017

Molecular Therapy - Methods & Clinical Development

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Lactococcus lactis is well documented as a promising candidate for development of novel oral live vaccines. It has been broadly engineered for heterologous expression, as well as for plasmid expression vector delivery, directly inside eukaryotic cells, for DNA vaccine, or as therapeutic vehicle. This work describes the characteristics of a new plasmid, pExu (extra chromosomal unit), for DNA delivery using L. lactis and evaluates its functionality both by in vitro and in vivo assays. This plasmid exhibits the following features: (1) a theta origin of replication and (2) an expression cassette containing a multiple cloning site and a eukaryotic promoter, the cytomegalovirus (pCMV). The functionality of pExu:egfp was evaluated by fluorescence microscopy. The L. lactis MG1363 (pExu:egfp) strains were administered by gavage to Balb/C mice and the eGFP expression was monitored by fluorescence microscopy. The pExu vector has demonstrated an excellent stability either in L. lactis or in Escherichia coli. The eGFP expression at different times in in vitro assay showed that 15.8% of CHO cells were able to express the protein after transfection. The enterocytes of mice showed the expression of eGFP protein. Thus, L. lactis carrying the pExu is a good candidate to deliver genes into eukaryotic cells.

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Section: Discussionmentioning

confidence: 99%

A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays

Mancha-Agresti

Drumond

Carmo

et al. 2017

Molecular Therapy - Methods & Clinical Development

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“…Engineered vaccines have benefited from an established regulatory framework and several such products are now in late-stage clinical development [see (Refs 10, 94) for more in-depth reviews].…”

Section: Clinical Applicationmentioning

confidence: 99%

Intracellular delivery of biologic therapeutics by bacterial secretion systems

Walker

Stan

Polizzi

2017

Expert Rev. Mol. Med.

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Biologics are a promising new class of drugs based on complex macromolecules such as proteins and nucleic acids. However, delivery of these macromolecules into the cytoplasm of target cells remains a significant challenge. Here we present one potential solution: bacterial nanomachines that have evolved over millions of years to efficiently deliver proteins and nucleic acids across cell membranes and between cells. In this review, we provide a brief overview of the different bacterial systems capable of direct delivery into the eukaryotic cytoplasm and the medical applications for which they are being investigated, along with a perspective on the future directions of this exciting field.

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“…Additionally, the attenuated vaccines can be used as vectors for vaccines against other infections or antitumor agents [2, 3]. Nevertheless, although the excellent safety of the licensed live vaccines had been demonstrated in a number of clinical investigations, there are health and biosafety concerns regarding the release of genetically modified bacteria into the environment [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Elimination of persistent vaccine bacteria of Salmonella enterica serovar Typhimurium in the guts of immunized mice by inducible expression of truncated YncE

Wang

Xiong

et al. 2017

PLoS ONE

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Orally administered vaccine bacteria usually persist for a period of time in the intestinal tracts of immunized individuals, and are excreted in feces to the environment resulting in a potential biosafety issue. The releasing risk can be minimized by immediate elimination of the persistent vaccine bacteria once adequate protective immune responses have been elicited by the vaccine bacteria. In a previous study, inducible expression of truncated yncE gene (yncE*) was found lethal to host bacteria. This feature has an application potential in biosafety control. Here, we assessed the efficacy of YncE* in eliminating an attenuated strain of Salmonella enterica serovar Typhimurium in a mouse model. To this end, a pBAD-derived plasmid containing yncE* under the control of the Ara promoter was transformed into a ΔphoPQ mutant of S. Typhimurium. Our data show that the induced expression of yncE* in the presence of arabinose eliminated the vaccine bacteria both in vitro and in vivo. BALB/c mice with or without streptomycin-pretreatment were used to assess the efficacy of YncE* in vivo. Oral administration of 500 μl of 20% arabinose at 24 h postvaccination removed the vaccine bacteria from the guts of the tested mice without streptomycin-pretreatment. For streptomycin-pretreated mice, which were colonized with higher levels of Salmonella, an additional gavage of arabinose was required to completely eliminate the vaccine bacteria in the guts of the tested mice. The orally administered arabinose did not affect the persistence of bacteria that had penetrated the intestinal mucosa of the immunized mice. Furthermore, there was no significant difference in the protection rate between the routine immunization and the immunization with the arabinose treatment. The results indicate that the yncE* element improves the biosafety of the bacterial vaccine, and can be taken in consideration in future design of live bacterial vaccines.

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Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

Cited by 93 publications

References 190 publications

A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays

A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays

Intracellular delivery of biologic therapeutics by bacterial secretion systems

Elimination of persistent vaccine bacteria of Salmonella enterica serovar Typhimurium in the guts of immunized mice by inducible expression of truncated YncE

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