A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges

Vinod, Nagarajan; Noh, Han Byul; Oh, Sung Jong; Ji, Seongmi; Park, Hyun Jung; Lee, Ki-Sung; Kim, Sei Chang; Park, Han-Oh; Yang, Joo-Sung; Choi, Chang Won

doi:10.1371/journal.pone.0185488

Cited by 21 publications

(10 citation statements)

References 57 publications

(66 reference statements)

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“…A multitude of vaccine development endeavors utilizing attenuated live bacteria, whole-cell killed vaccines, and subunit vaccines aimed at inducing long-term, cross protective immunity against multiple Salmonella NTS serovars are underway [ 6 – 10 ]. The ability of live attenuated Salmonella strains to stimulate strong humoral and cellular immunity has rendered them as an attractive option for development as homologous vaccines and for use as carriers of heterologous antigens [ 11 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence

et al. 2018

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The initial virulence and invasiveness of a bacterial strain may play an important role in leading to a maximally efficacious attenuated live vaccine. Here we show that χ9909, derived from Salmonella Typhimurium UK-1 χ3761 (the most virulent S. Typhimurium strain known to us), is effective in protecting mice against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge. As opposed to this, 14028S-derived vaccine χ12359 induces suboptimal levels of protection, with survival percentages that are significantly lower when challenged with lethal UK-1 challenge doses. T-cell assays have revealed that significantly greater levels of Th1 cytokines IFN-γ and TNF-α were secreted by stimulated T-lymphocytes obtained from UK-1(ΔaroA) immunized mice than those from mice immunized with 14028S(ΔaroA). In addition, UK-1(ΔaroA) showed markedly higher colonizing ability in the spleen, liver, and cecum when compared to 14028S(ΔaroA). Enumeration of bacteria in fecal pellets has also revealed that UK-1(ΔaroA) can persist in the host for over 10 days whereas 14028S(ΔaroA) titers dropped significantly by day 10. Moreover, co-infection of parent strains UK-1 and 14028S resulted in considerably greater recovery of the former in multiple mucosal and gut associated lymphatic tissues. Mice immunized with UK-1(ΔaroA) were also able to clear UK-1 infection remarkably more efficiently from the target organs than 14028S(ΔaroA). Together, these results provide ample evidence to support the hypothesis that attenuated derivatives of parent strains with higher initial virulence make better vaccines.

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Section: Introductionmentioning

confidence: 99%

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence

et al. 2018

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“…After the tunnel structure forms, bacterial cytoplasm is released into the extracellular environment, leaving behind cell envelopes known as BGs (Witte & Lubitz, 1989; Witte et al, 1990). Since this process does not cause any denaturation to envelope structures, one of the main characteristics of BGs is the preservation of surface immunostimulatory elements, such as LPS, peptidoglycan, and flagella, showing a potential for BGs used as a candidate vaccine against respective pathogens (Hoseini Shahidi et al, 2019; Vinod et al, 2017). Moreover, BGs with the perfect adjuvant activity and a high loading capacity can serve as a carrier for delivery of heterologous antigens and DNA vaccines (Hajam et al, 2017).…”

Section: Bacterial Derivatives For Cancer Therapymentioning

confidence: 99%

New technologies in developing recombinant‐attenuated bacteria for cancer therapy

Liang

Liu

Kong

2020

Biotech & Bioengineering

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Cancer has always been a global problem, with more cases of cancer patients being diagnosed every year. Conventional cancer treatments, including radiotherapy, chemotherapy, and surgery, are still unable to bypass their obvious limitations, and developing effective targeted therapies is still required. More than one century ago, the doctor William B. Coley discovered that cancer patients had tumor regression by injection of Streptococcus bacteria. The studies of cancer therapy using bacterial microorganisms are now very widespread. In particular, the facultative anaerobic bacteria Salmonella typhimurium is widely investigated as it can selectively colonize different types of tumors, locally deliver various antitumor drugs, and inhibit tumor growth. The exciting antitumor efficacy and safety observed in animal tumor models prompted the well‐known attenuated Salmonella bacterial strain VNP20009 to be tested in human clinical trials in the early 21st century. Regrettably, no patients showed significant therapeutic effects and even bacterial colonization in tumor tissue was undetectable in most patients. Salmonella bacteria are still considered as a promising agent or vehicle for cancer therapy. Recent efforts have been focused on the generation of attenuated bacterial strains with higher targeting for tumor tissue, and optimization of the delivery of therapeutic antitumor cargoes into the tumor microenvironment. This review will summarize new technologies or approaches that may improve bacteria‐mediated cancer therapy.

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“…Integration of the 91 amino-acid polypeptide E in the bacterial envelope triggers a fusion process of the inner and outer membranes to form a transmembrane tunnel structure through which the cytoplasmic content is expelled driven by a proton-motive force (28, 29). To date, BG have been made from a variety of pathogens including Escherichia coli K12 (30), enterotoxigenic and enterohemaorrhagic E. coli (EHEC, ETEC) (31), Helicobacter pylori (32), Salmonella typhimurium (33), S. enteritidis (34), and Vibrio cholerae (35) for both veterinary and clinical vaccine purposes. BG have also been evaluated as drug delivery (36) and adjuvant (37) systems.…”

Section: Introductionmentioning

confidence: 99%

Harnessing the Immunomodulatory Properties of Bacterial Ghosts to Boost the Anti-mycobacterial Protective Immunity

et al. 2019

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Tuberculosis (TB) pathogenesis is characterized by inadequate immune cell activation and delayed T cell response in the host. Recent immunotherapeutic efforts have been directed at stimulating innate immunity and enhancing interactions between antigen presenting cells and T cells subsets to improve the protective immunity against TB. In this study, we investigated the immunostimulatory properties of bacterial ghosts (BG) as a novel approach to potentiate the host immunity against mycobacterial infection. BG are intact cytoplasm-free Escherichia coli envelopes and have been developed as bacterial vaccines and adjuvant/delivery system in cancer immunotherapy. However, BG have yet to be exploited as immunopotentiators in the context of infectious diseases. Here, we showed that BG are potent inducers of dendritic cells (DC), which led to enhanced T cell proliferation and differentiation into effector cells. BG also induced macrophage activation, which was associated with enhanced nitric oxide production, a key anti-mycobacterial weapon. We further demonstrated that the immunostimulatory capability of BG far exceeds that of LPS and involves both TLR4-dependent and independent pathways. Consistently, BG treatment, but not LPS treatment, reduced the bacterial burden in infected mice, which correlated with increased influx of innate and adaptive effector immune cells and increased production of key cytokines in the lungs. Finally and importantly, enhanced bacilli killing was seen in mice co-administered with BG and second-line TB drugs bedaquiline and delamanid. Overall, this work paves the way for BG as potent immunostimulators that may be harnessed to improve mycobacteria killing at the site of infection.

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A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges

Cited by 21 publications

References 57 publications

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence

New technologies in developing recombinant‐attenuated bacteria for cancer therapy

Harnessing the Immunomodulatory Properties of Bacterial Ghosts to Boost the Anti-mycobacterial Protective Immunity

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