Modulation of the Immune System by <i>Listeria monocytogenes</i>‐Mediated Gene Transfer into Mammalian Cells

Shen, Hua; Kanoh, Makoto; Liu, Fengzhi; Maruyama, Saho; Asano, Yoshihiro

doi:10.1111/j.1348-0421.2004.tb03514.x

Cited by 18 publications

(15 citation statements)

References 34 publications

(37 reference statements)

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“…Not every protein is likely to be secreted by Listeria, and it might be difficult for prokaryotes to express sufficient amounts of proteins of eukaryotic origin without optimization of codon usage (39). Other therapeutic approaches, in which Listeria can be utilized as a carrier for the delivery of, e.g., cytokines in order to modulate immune responses (32), might be possible only by transfer of cytokine-encoding nucleic acids, since so far cytokines cannot be functionally expressed by prokaryotes. Accordingly, for the delivery of prodrug-converting enzymes by L. monocytogenes in the context of gene-directed enzyme prodrug therapy of tumor tissue (J. Stritzker, submitted for publication), the delivery of enzyme-encoding DNA was shown to be superior to the delivery of a secreted enzyme, at least in vitro, showing that there are challenges for every Listeria-based delivery strategy.…”

Section: Discussionmentioning

confidence: 99%

“…Listeria monocytogenes, a gram-positive bacterium, has been used successfully in several studies performed with different animal models to deliver tumor, viral, or parasite antigens, as well as different cytokines either as secreted protein (13,23,34) or as plasmid-encoded DNA (21,32,35). A number of biological properties make L. monocytogenes a promising platform for the development of vaccines, particularly vaccines against infectious diseases or tumors.…”

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confidence: 99%

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Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-AttenuatedListeria monocytogenes

et al. 2006

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Listeria monocytogenes can be used to deliver protein antigens or DNA and mRNA encoding such antigens directly into the cytosol of host cells because of its intracellular lifestyle. In this study, we compare the in vivo efficiencies of activation of antigen-specific CD8 and CD4 T cells when the antigen is secreted by L. monocytogenes or when antigen-encoding plasmid DNA or mRNA is released by self-destructing strains of L. monocytogenes. Infection of mice with self-destructing L. monocytogenes carriers delivering mRNA that encodes a nonsecreted form of ovalbumin (OVA) resulted in a significant OVA-specific CD8 T-cell response. In contrast, infection with L. monocytogenes delivering OVA-encoding DNA failed to generate specific T cells. Secretion of OVA by the carrier bacteria yielded the strongest immune response involving OVA-specific CD8 and CD4 T cells. In addition, we investigated the antigen delivery capacity of a self-destructing, virulence-attenuated L. monocytogenes aroA/B mutant. In contrast to the wild-type strain, this mutant exhibited only marginal liver toxicity when high doses (5 ؋ 10 7 CFU per animal administered intravenously) were used, and it was also able to deliver sufficient amounts of secreted OVA into mice. Therefore, the results presented here could lay the groundwork for a rational combination of L. monocytogenes as an attenuated carrier for the delivery of protein and nucleic acid vaccines in novel vaccination strategies.The use of virulence-attenuated bacteria as carriers for heterologous protein antigens is a versatile vaccination approach (for a review see reference 15). Bacteria directly target vaccine antigens to the appropriate cells of the immune system, such as dendritic cells (DC), for antigen presentation (17), and they act as strong immune potentiators due to their naturally produced bacterial components (pathogen-associated molecular patterns) that stimulate and modulate early innate immune responses, encouraging the generation of robust and long-lasting adaptive immune responses (11).In the majority of cases so far, virulence-attenuated strains of enteric bacterial pathogens like Salmonella, Shigella, Yersinia, Vibrio, Escherichia coli, or Listeria have been used for vaccine delivery (15). These bacteria, which can be inoculated orally, are able to cross the intestinal mucosa and induce systemic immunity as well as mucosal immunity. Therefore, virulence-attenuated bacteria are optimal candidates as carriers for heterologous protein antigens, antigen-encoding DNA (DNA vaccines), and other molecules for vaccination or other therapeutic purposes (15).In particular, the bacteria that are able to replicate and release antigen within the cytosol of eukaryotic host cells are attractive candidates for the elicitation of cell-mediated immunity against heterologous antigens. Listeria monocytogenes, a gram-positive bacterium, has been used successfully in several studies performed with different animal models to deliver tumor, viral, or parasite antigens, as well as different cytokines...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-AttenuatedListeria monocytogenes

et al. 2006

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“…The study was conducted in vitro and in vivo in mice, but despite promising results this method has not been tested clinically yet. 12 Also, protection against lethal doses of L. monocytogenes infection in mice after multiple application of S. typhimurium-carrying plasmid-encoding LLO from L. monocytogenes as a antigen was described. 32 Bactofection can also be used for DNA vaccination against numerous microbial agents including viruses, parasitical protozoa, fungi and even other bacteria.…”

Section: Experimental and Clinical Studies Bactofectionmentioning

confidence: 99%

Bacteria in gene therapy: bactofection versus alternative gene therapy

et al. 2005

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Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for gene therapy applications. In this article we try to summarize the most important modifications that are used for the preparation of applied strains, difficulties that are related with bacterial gene delivery and the current use of bactofection in animal experiments and clinical trials. Important differences to the alternative gene therapy (AGT) are discussed. AGT resembles bacteria-mediated protein delivery, as the therapeutical proteins are produced not by host cells but by the bacteria in situ and the expression can be regulated exogenously. Although the procedure of bacterial gene delivery is far from being definitely solved, bactofection remains a promising technique for transfection in human gene therapy.

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“…One strategy to achieve intracellular rupture of the bacteria is through the use of cell-walldeficient bacteria, an approach that has been examined in Gramnegative bacteria such as E. coli and Shigella (4)(5)(6)(7)(8). Due the intracellular life cycle of Listeria monocytogenes (9), this Grampositive bacterium also has been examined as a DNA delivery vector for immune modulation or gene therapy (10)(11)(12)(13)(14)(15). These previous systems have used wild-type L. monocytogenes (10,16), bacteria that express reduced hemolysin activity (12), or bacteria that express the lytic protein from bacteriophage A118 (11,(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Plasmid DNA Delivery by d‐Alanine‐Deficient Listeria monocytogenes

Simon¹,

Ybarra²,

Bonneval³

et al. 2006

Biotechnology Progress

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Optimal DNA vaccine efficacy requires circumventing several obstacles, including low immunogenicity, a need for adjuvant, and the costs of purifying injection grade plasmid DNA. Bacterial delivery of plasmid DNA may provide an efficient and low-cost alternative to plasmid purification and injection. Also, the bacterial vector may exhibit potential as an immune adjuvant in vivo. Thus, we elected to examine the use of cell-wall-deficient Listeria monocytogenes as a DNA delivery vehicle in vitro. First, the D-alanine-deficient (Deltadal-dat) L. monocytogenes strain DP-L3506, which undergoes autolysis inside eukaryotic host cells in the absence of D-alanine, was transformed with a plasmid encoding green fluorescent protein (GFP) under control of the CMV promoter (pAM-EGFP). Then COS-7 and MC57G cell lines were infected with the transformed DP-L3506 at various multiplicities of infection (MOI) in the presence or absence of D-alanine. Subsequent GFP expression was observed in both cell lines by 24 h post-infection with DP-L3506(pAM-EGFP). Notably, no GFP positive cells were observed when D-alanine was omitted. Although transfection efficiency initially increased as a result of D-alanine supplementation, high concentration or long-term supplementation led to sustained bacterial growth that killed the infected host cells, resulting in fewer GFP-expressing cells. Thus, efficient DNA delivery by transformed bacteria must balance bacterial invasion and survival with target cell health and survival.

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Modulation of the Immune System by Listeria monocytogenes‐Mediated Gene Transfer into Mammalian Cells

Cited by 18 publications

References 34 publications

Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-AttenuatedListeria monocytogenes

Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-AttenuatedListeria monocytogenes

Bacteria in gene therapy: bactofection versus alternative gene therapy

Plasmid DNA Delivery by d‐Alanine‐Deficient Listeria monocytogenes

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