phoP/phoQ-Deleted Salmonella typhi (Ty800) Is a Safe and Immunogenic Single Dose Typhoid Fever Vaccine in Volunteers

Hohmann, Elizabeth L.; Oletta, Carmen A.; Killeen, Kevin; Miller, Samuel I.

doi:10.1093/infdis/173.6.1408

Cited by 250 publications

(180 citation statements)

References 27 publications

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“…30 The human PCa cell line DU145 was obtained from ATCC (American Type Culture Collection, Manassas, VA, USA) and grown in RPMI-1640 (Life Technologies, Inc, Gaithersburg, MD, USA) supplemented with 10% fetal bovine serum. For transfection, cells were plated into a 100-mm dish (10 6 cells) and allowed to adhere for 24 h. LipofectAMINE 2000 (Invitrogen, Carlsbad, CA, USA) was used for transfection.…”

Section: Construction Of Recombinant Plasmidsmentioning

confidence: 99%

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Liu

Zhang²,

Guo³

et al. 2012

Asian J Androl

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Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.

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Section: Construction Of Recombinant Plasmidsmentioning

confidence: 99%

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Liu

Zhang²,

Guo³

et al. 2012

Asian J Androl

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“…In human trials, Ty800 induced high-level immune responses with a single dose and without adverse side effects, except for diarrhea in a small number of individuals (58). Phase I/II clinical trials were undertaken by AVANT Immunotherapeutics, Inc. which aimed at determining the safety and immunogenicity of the single-dose, oral Ty800 vaccine.…”

Section: Therapeutic Measures To Salmonella Typhi Infections and The mentioning

confidence: 99%

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

2008

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Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular & Molecular Immunology. 2008;5(2):91-97.

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“…However, both vaccines have drawbacks that necessitate the development of next-generation typhoid vaccines: Ty21a requires 3 or 4 oral doses, while Vi requires a needle injection, and refrigeration is necessary for both (13,14). Several next-generation vaccines, designed to optimize efficacy and simplify delivery, are currently in human trials, including a single-oral-dose typhoid vaccine, M01ZH09 (S. Typhi Ty2 ⌬aroC ⌬ssaV) (4,14,17,22,28,31,32,41).…”

mentioning

confidence: 99%

Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi

et al. 2011

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Although vaccines have been available for over a century, a correlate of protection for typhoid fever has yet to be identified. Antibodies are produced in response to typhoid infection and vaccination and are generally used as the gold standard for determining vaccine immunogenicity, even though their role in clearance of Salmonella enterica serovar Typhi infections is poorly defined. Here, we describe the first functional characterization of S. Typhi-specific antibodies following vaccination with a new vaccine, M01ZH09 (Ty2 ⌬aroC ⌬ssaV). We determined that postvaccination sera increased the uptake of wild-type S. Typhi by human macrophages up to 2.3-fold relative to prevaccination (day 0) or placebo samples. These results were recapitulated using immunoglobulins purified from postvaccination serum, demonstrating that antibodies were largely responsible for increases in uptake. Imaging verified that macrophages internalized 2-to 9.5-fold more S. Typhi when the bacteria were opsonized with postvaccination sera than when the bacteria were opsonized with day 0 or placebo sera. Once inside macrophages, the survival of S. Typhi was reduced as much as 50% when opsonized with postvaccination sera relative to day 0 or placebo serum samples. Lastly, bactericidal assays indicated that antibodies generated postvaccination were recognized by complement factors and assisted in killing S. Typhi: mean postvaccination bactericidal antibody titers were higher at all time points than placebo and day 0 titers. These data clearly demonstrate that there are at least two mechanisms by which antibodies facilitate killing of S. Typhi. Future work could lead to improved immunogenicity tests associated with vaccine efficacy and the identification of correlates of protection against typhoid fever.

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phoP/phoQ-Deleted Salmonella typhi (Ty800) Is a Safe and Immunogenic Single Dose Typhoid Fever Vaccine in Volunteers

Cited by 250 publications

References 27 publications

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi

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