Oral delivery of DNA vaccines using attenuated<i>Salmonella typhimurium</i>as carrier

Darji, Ayub; Lage, Susanne zur; Garbe, Annette I.; Chakraborty, Trinad; Weiß, Siegfried

doi:10.1111/j.1574-695x.2000.tb01448.x

Cited by 109 publications

(13 citation statements)

References 37 publications

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“…Similar effects were found when Salmonella was used for oral vaccination. Both, humoral and cellular antigen-specific immunity were confirmed in several mouse strains (79,80). Beyond immunological reasons bacteria-mediated DNA vaccination is usable also due to relatively cheap production costs.…”

Section: Dna Vaccinationmentioning

confidence: 85%

Gene therapy using bacterial vectors

Celec

Gardlík

2017

Front Biosci

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Bacteria can be used for gene therapy via two strategies - either by transfection of eukaryotic host cells using bacteria (bactofection) or by alternative gene therapy that does not alter the host genome, but uses the prokaryotic expression system, which can be controlled or stopped from outside. While bactofection is optimal for gene substitution and DNA vaccination, alternative gene therapy is suitable for delivery of proteins and treatment with intracellular bactochondria. A specific form of bacteria-mediated gene therapy is transkingdom RNA interference. In this review, advantages and issues related to bacterial vectors as well as the major applications in biomedical research are summarized. Despite numerous published experiments, especially in the treatment of solid tumors and gut infections, progress in the clinics lags behind and major improvements in the safety, and even more in the efficiency, of these approaches are needed.

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Section: Dna Vaccinationmentioning

confidence: 85%

Gene therapy using bacterial vectors

Celec

Gardlík

2017

Front Biosci

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“…Strategies aimed to elicit optimized effector CD8 + T cell response, in a way that single antigen-specific clones may present multiple effector functions and differentiate to longlived memory T cells, have been proposed (35). Among such strategies, the use of intracellular infectious bacteria carrying single or multiple therapeutic proteins holds promise (36,37). In fact, it has been previously reported that recombinant L. monocytogenes carrying the ovalbumin gene (LM-OVA) induces strong OVA-specific CD8 + T cell response and protects mice against B16-OVA melanoma cell line (38).…”

Section: Discussionmentioning

confidence: 99%

RIPK3 and Caspase-1/11 Are Necessary for Optimal Antigen-Specific CD8 T Cell Response Elicited by Genetically Modified Listeria monocytogenes

et al. 2020

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Efficient induction of effector and long-term protective antigen-specific CD8 + T memory response by vaccination is essential to eliminate malignant and pathogen-infected cells. Intracellular infectious bacteria, including Listeria monocytogenes, have been considered potent vectors to carry multiple therapeutic proteins and generate antigenspecific CD8 + T cell responses. Although the role of molecules involved in inflammatory cell death pathways, such as necroptosis (RIPK3-mediated) and pyroptosis (Caspase-1/11-mediated), as effectors of immune response against intracellular bacteria are relatively well understood, their contribution to the adjuvant effect of recombinant bacterial vectors in the context of antigen-specific CD8 + T cell response remained obscure. Therefore, we evaluated the impact of RIPK3 and Caspase-1/11 (Casp-1/11) individual and combined deficiencies on the modulation of antigen-specific CD8 + T cell response during vaccination of mice with ovalbumin-expressing L. monocytogenes (LM-OVA). We observed that Casp-1/11 but not RIPK3 deficiency negatively impacts the capacity of mice to clear LM-OVA. Importantly, both RIPK3 and Casp-1/11 are necessary for optimal LM-OVA-mediated antigen-specific CD8 + T cell response, as measured by in vivo antigen-specific CD8 + T cell proliferation, target cell elimination, and cytokine production. Furthermore, Casp-1/11 and Casp-1/11/RIPK3 combined deficiencies restrict the early initiation of antigen-specific CD8 + T cell memory response. Taken together, our findings demonstrate that RIPK3 and Casp-1/11 influence the quality of CD8 + T cell responses induced by recombinant L. monocytogenes vectors.

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“…A DNA delivery system has the advantage, over traditional naked DNA vaccination, that bacteria protect the DNA vaccine from the environment until it reaches the macrophages, where the Salmonella is disrupted, releasing its intracellular plasmid cargo and enabling expression of the recombinant protein by the eukaryotic cell machinery. It was previously shown that oral immunization with this system is able to induce specific antibody and cellular responses, with Th1 and CD8 ϩ cell activation, as well as specific mucosal immunity (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

et al. 2014

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In this work we immunized mice with DNA encoding full-length Tc52 or its amino-or carboxy-terminal (N-and C-term, respectively) domain carried by attenuated Salmonella as a DNA delivery system. As expected, Salmonella-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All immunized groups developed strong cellular responses, with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-␥ ؉ ) CD8 ؉ T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.

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Oral delivery of DNA vaccines using attenuatedSalmonella typhimuriumas carrier

Cited by 109 publications

References 37 publications

Gene therapy using bacterial vectors

Gene therapy using bacterial vectors

RIPK3 and Caspase-1/11 Are Necessary for Optimal Antigen-Specific CD8 T Cell Response Elicited by Genetically Modified Listeria monocytogenes

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

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