Oral administration of a Bacillus subtilis spore-based vaccine expressing Clonorchis sinensis tegumental protein 22.3kDa confers protection against Clonorchis sinensis

Zhou, Zhenwen; Xia, Huimin; Hu, Xuchu; Huang, Yan; Li, Yanwen; Li, Li; Ma, Chao; Chen, Xiaoxiang; Hu, Fengyu; Xu, Jin; Lü, Fangli; Wu, Zhongdao; Yu, Xinbing

doi:10.1016/j.vaccine.2008.02.015

Cited by 85 publications

(72 citation statements)

References 36 publications

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“…In addition, B. subtilis spores can be easily engineered to display, on their surface, a large variety of heterologous antigens in association with spore coat proteins. The spore coat proteins CotB and CotC have already been used as fusion partners for various proteins, such as the tetanus toxin fragment C (TTFC) , the B subunit of the heat-labile toxin of Escherichia coli (LTB) (Mauriello et al, 2004), the protective antigen (PA) of Bacillus anthracis (le Duc et al, 2007), and the Clonorchis sinensis 22.3 kDa tegumental protein (CsTP22.3) (Zhou et al, 2008). Immunization of mice with B. subtilis spores displaying TTFC, PA or CsTP22.3 was shown to induce a protective immune response against a challenge with the tetanus toxin, B. anthracis spores or C. sinensis, respectively (le Duc et al, 2003bDuc et al, , 2007Zhou et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…The spore coat proteins CotB and CotC have already been used as fusion partners for various proteins, such as the tetanus toxin fragment C (TTFC) , the B subunit of the heat-labile toxin of Escherichia coli (LTB) (Mauriello et al, 2004), the protective antigen (PA) of Bacillus anthracis (le Duc et al, 2007), and the Clonorchis sinensis 22.3 kDa tegumental protein (CsTP22.3) (Zhou et al, 2008). Immunization of mice with B. subtilis spores displaying TTFC, PA or CsTP22.3 was shown to induce a protective immune response against a challenge with the tetanus toxin, B. anthracis spores or C. sinensis, respectively (le Duc et al, 2003bDuc et al, , 2007Zhou et al, 2008). Nevertheless, information on the interaction of B. subtilis spores with human macrophages is lacking, while this step has a crucial role in both controlling the initial host colonization/invasion by infectious agents and in instructing the adaptive immune response by presenting pathogen-derived peptides to local T-cells .…”

Section: Introductionmentioning

confidence: 99%

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Phagocytosis, germination and killing of Bacillus subtilis spores presenting heterologous antigens in human macrophages

et al. 2009

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Bacillus subtilis is a Gram-positive spore-bearing bacterium long used as a probiotic product and more recently regarded as an attractive vehicle for delivering heterologous antigens to be used for mucosal vaccination. This report describes the in vitro interaction between human macrophages and B. subtilis spores displaying the tetanus toxin fragment C or the B subunit of the heat-labile toxin of Escherichia coli on their surface in comparison to spores of the parental strain. Recombinant and parental B. subtilis spores were similarly internalized by human macrophages, at a frequency lower than 2.5 %. Inside macrophages, nearly all spores germinated and were killed within 6 h. Using germination-defective spores and inhibiting spore germination inside macrophages, evidence was produced that only germinated spores were killed by human macrophages and that intracellular spore germination was mediated by an alanine-dependent pathway. The germinated spores were killed by macrophages before any round of cell duplication, as estimated by fluorescence microscopy analysis of macrophages infected with spores carrying the gfp gene fused to abrB, a B. subtilis gene shown here to be expressed at the transition between outgrowth and vegetative growth. Monitoring of macrophage infection never revealed cytotoxic effects being exerted by B. subtilis spores. These in vitro data support the hypothesis that B. subtilis spores may potentially be used as a suitable and safe vehicle for administering heterologous antigens to humans.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phagocytosis, germination and killing of Bacillus subtilis spores presenting heterologous antigens in human macrophages

et al. 2009

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“…[43][44][45][46][47] We have demonstrated that B. subtilis vegetative cells and spores engineered to express tetanus toxin fragment C (TetC) can induce protective immunity in mice and piglets, and when stored as lyophilized powders, have long-term stability during storage at elevated temperatures. 6,32,38 In these experiments, these vaccines are effective when administered either intranasally or sublingually.…”

Section: Using Recombinant B Subtilis As Vaccine Delivery Vehiclementioning

confidence: 99%

Bacillus subtilis

Amuguni

Tzipori

2012

Human Vaccines & Immunotherapeutics

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Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success.As discussed in this review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases.

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“…In both cases, the antigen-displaying spores provoked an immune response in mice, when they were delivered by intra-peritoneal injection or by oral administration. A Chinese group published two related reports for the development of spore-based vaccines against human clonorchiasis using CotC as an anchoring motif [91,92]. Caused by infection with the nematode of C. sinensis, clonorchiasis is endemic in southern China [93], Korea, and other southeast Asian countries.…”

Section: Composition Of the B Subtilis Endosporementioning

confidence: 99%

“…By large-scale sequencing of a C. sinensis cDNA library, they had identified three full-length cDNAs encoding three putative tegumental proteins (TP20.8, TP22.3, TP31.8), which could be the most susceptible target for vaccines because of their importance for the host response and parasite survival. Among them, they performed parallel study with TP20.8 [94] and TP22.3 [91]. In both cases, when antigen-displaying spores were delivered orally, they reported an elevated secretory level of IgA, which aggregated pathogens, inhibited their motility, and prevented their adherence to epithelial cells.…”

Section: Composition Of the B Subtilis Endosporementioning

confidence: 99%

Display of proteins on Bacillus subtilis endospores

Kim

Schumann

2009

Cell. Mol. Life Sci.

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The targeting and anchoring of heterologous proteins and peptides to the outer surface of bacteriophages and cells is becoming increasingly important, and has been employed as a tool for fundamental and applied research in microbiology, molecular biology, vaccinology, and biotechnology. Less known are endospores or spores produced by some Gram-positive species. Spores of Bacillus subtilis are surrounded by a spore coat on their outside, and a few proteins have been identified being located on the outside layer and have been successfully used to immobilize antigens and some other proteins and enzymes. The major advantage of spores over the other published systems is their synthesis within the cytoplasm of the bacterial cell. Therefore, any heterologous protein to be anchored on the outside does not have to cross any membrane. Furthermore, spores are extremely resistant against high temperature, irradiation and many chemicals, and can be stored for many years at room temperature.

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Oral administration of a Bacillus subtilis spore-based vaccine expressing Clonorchis sinensis tegumental protein 22.3kDa confers protection against Clonorchis sinensis

Cited by 85 publications

References 36 publications

Phagocytosis, germination and killing of Bacillus subtilis spores presenting heterologous antigens in human macrophages

Phagocytosis, germination and killing of Bacillus subtilis spores presenting heterologous antigens in human macrophages

Bacillus subtilis

Display of proteins on Bacillus subtilis endospores

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