Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83.

Abstract:

:Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, MPT-64 and MPT-83 protected mice from TB following H37Rv challenge and considered whether this combined DNA vaccine has a therapeutic effect. In the present work, we demonstrate that boosting the efficiency of the immune system with the combined DNA vaccine may be a valuable adjunct to shorten the duration of antibacterial chemotherapy. Mice treated with the combined DNA vaccine along with isoniazid and pyrazinamide showed significantly higher interferon-gamma responses to a mixture of the three specific antigens (P<0.001), which were accompanied by a significant reduction in colony-forming unit in H37Rv-infected animals 3-5 months after treatment (P<0.001). These results suggest that the combined DNA vaccine along with conventional TB chemotherapy has strong potential for TB immunotherapy and may provide new alternatives to control the disease.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Yu DH,Hu XD,Cai H

doi

10.1038/gt.2008.13

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

652-9

issue

9

eissn

0969-7128

issn

1476-5462

pii

gt200813

journal_volume

15

pub_type

杂志文章
  • Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs.

    abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303055

    authors: Choy EY,Kok KH,Tsao SW,Jin DY

    更新日期:2008-02-01 00:00:00

  • A novel, membrane receptor-based retroviral vector for Fanconi anemia group C gene therapy.

    abstract::Retroviral vectors are effective shuttle systems by introducing therapeutically relevant genes stably into the genome of proliferating cells. The majority of vectors applied for research or clinical applications use neomycin for cell selection and identification. To circumvent the time consuming and potentially toxic ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300384

    authors: Machl AW,Planitzer S,Kubbies M

    更新日期:1997-04-01 00:00:00

  • Multiple systemic expression of human interferon-beta in mice can be achieved upon repeated administration of optimized pcTG90-lipoplex.

    abstract::The possibility of achieving multiple systemic expression of human interferon-beta in mice upon repeated intravenous administration of cationic liposome-DNA complex (lipoplex) was investigated. Lipoplexes containing the pentammonio lipid pcTG90 were first optimized by selecting the most efficient ratio of pcTG90 to ph...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301289

    authors: Meyer O,Schughart K,Pavirani A,Kolbe HV

    更新日期:2000-09-01 00:00:00

  • Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector.

    abstract::One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor f...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300974

    authors: Nathwani AC,Persons DA,Stevenson SC,Frare P,McClelland A,Nienhuis AW,Vanin EF

    更新日期:1999-08-01 00:00:00

  • The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication.

    abstract::The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300784

    authors: Touraine RL,Ishii-Morita H,Ramsey WJ,Blaese RM

    更新日期:1998-12-01 00:00:00

  • Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes.

    abstract::Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates blood glucose level post-prandially. It has been proposed that GLP-1 can be used in type 2 diabetes (T2D) mellitus treatment because of its insulinotropic action. Despite its remarkable advantages, GLP-1 suffers the disadvantage of an extremely shor...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.25

    authors: Jean M,Alameh M,Buschmann MD,Merzouki A

    更新日期:2011-08-01 00:00:00

  • Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

    abstract::Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leadin...

    journal_title:Gene therapy

    pub_type: 信件,评审

    doi:10.1038/s41434-018-0004-0

    authors: Sampara P,Banala RR,Vemuri SK,Av GR,Gpv S

    更新日期:2018-04-01 00:00:00

  • Understanding lentiviral vector chromatin targeting: working to reduce insertional mutagenic potential for gene therapy.

    abstract::Replication-deficient retroviruses have been successfully utilized as vectors, offering an efficient, stable method of therapeutic gene delivery. Many examples exist proving this mode of integrative gene transfer is both effective and safe in cultured systems and clinical trials. Along with their success, severe side ...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2012.88

    authors: Papayannakos C,Daniel R

    更新日期:2013-06-01 00:00:00

  • Correction of ornithine-delta-aminotransferase deficiency in a Chinese hamster ovary cell line mediated by retrovirus gene transfer.

    abstract::Gyrate atrophy (GA) of the choroid and retina is an autosomal recessive chorioretinal degeneration, caused by deficiency of the mitochondrial matrix enzyme ornithine-delta-aminotransferase (OAT). This deficiency results in the accumulation of ornithine in the body fluids and leads to hyperornithinemia. Although the cl...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Lacorazza HD,Jendoubi M

    更新日期:1995-01-01 00:00:00

  • RNA knockdown as a potential therapeutic strategy in Parkinson's disease.

    abstract::Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal mode...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302669

    authors: Manfredsson FP,Lewin AS,Mandel RJ

    更新日期:2006-03-01 00:00:00

  • A novel magnetic approach to enhance the efficacy of cell-based gene therapies.

    abstract::Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enh...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.57

    authors: Muthana M,Scott SD,Farrow N,Morrow F,Murdoch C,Grubb S,Brown N,Dobson J,Lewis CE

    更新日期:2008-06-01 00:00:00

  • Cultured human myoblasts and myotubes show markedly different transducibility by replication-defective adenovirus recombinants.

    abstract::Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into certain target cells, such as skeletal muscle cells for gene therapy. Here we show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV) recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can ve...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Acsadi G,Jani A,Huard J,Blaschuk K,Massie B,Holland P,Lochmüller H,Karpati G

    更新日期:1994-09-01 00:00:00

  • Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes.

    abstract::Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events. The present study tested if the ex vivo transfer of EC-SOD and catalase genes alone or in combi...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301916

    authors: Dai L,Claxson A,Marklund SL,Feakins R,Yousaf N,Chernajovsky Y,Winyard PG

    更新日期:2003-04-01 00:00:00

  • Blunting of immune responses to adenoviral vectors in mouse liver and lung with CTLA4Ig.

    abstract::Adenoviral vectors deleted of E1 are attractive vehicles for in vivo gene therapy because efficient gene transfer can be achieved. Immune responses to the vector and vector-transduced cells lead to destruction of target cells, inflammation and difficulties with vector readministration. Immune effectors have been ident...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300595

    authors: Jooss K,Turka LA,Wilson JM

    更新日期:1998-03-01 00:00:00

  • Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats.

    abstract::Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.183

    authors: Ogura M,Urabe M,Akimoto T,Onishi A,Ito C,Ito T,Tsukahara T,Mizukami H,Kume A,Muto S,Kusano E,Ozawa K

    更新日期:2012-05-01 00:00:00

  • Targeted gene transfer to corneal endothelium in vivo by electric pulse.

    abstract::A novel method of in vivo targeted gene transfer to intentionally selected areas of the corneal endothelium was developed. Plasmid DNA with the lacZ gene coding for beta-galactosidase was injected into the anterior chamber of adult Wistar rats, and eight pulses of electricity at intensities ranging from 5 to 40 V/cm w...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300725

    authors: Oshima Y,Sakamoto T,Yamanaka I,Nishi T,Ishibashi T,Inomata H

    更新日期:1998-10-01 00:00:00

  • Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme inhibits retinal neovascularization.

    abstract::Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of prolife...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302718

    authors: Shaw LC,Pan H,Afzal A,Calzi SL,Spoerri PE,Sullivan SM,Grant MB

    更新日期:2006-05-01 00:00:00

  • Genetic design of an optimized packaging cell line for gene vectors transducing human B cells.

    abstract::Viral gene vectors often rely on packaging cell lines, which provide the necessary factors in trans for the formation of virus-like particles. Previously, we reported on a first-generation packaging cell line for gene vectors, which are based on the B-lymphotropic Epstein-Barr virus (EBV), a human gamma-herpesvirus. T...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302714

    authors: Hettich E,Janz A,Zeidler R,Pich D,Hellebrand E,Weissflog B,Moosmann A,Hammerschmidt W

    更新日期:2006-05-01 00:00:00

  • Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer.

    abstract::A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure-activity relationship as gene carriers. We show that pseudodendritic core character...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303046

    authors: Russ V,Elfberg H,Thoma C,Kloeckner J,Ogris M,Wagner E

    更新日期:2008-01-01 00:00:00

  • Progress and prospects: oligonucleotide-directed gene modification in mouse embryonic stem cells: a route to therapeutic application.

    abstract::Gene targeting by single-stranded oligodeoxyribonucleotides (ssODNs) is a promising technique for introducing site-specific sequence alterations without affecting the genomic organization of the target locus. Here, we discuss the significant progress that has been made over the last 5 years in unraveling the mechanism...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2010.161

    authors: Aarts M,te Riele H

    更新日期:2011-03-01 00:00:00

  • HSV1 vectors to study protein targeting in neurones: are glycosyl-phosphatidylinositol anchors polarized targeting signals in neurones?

    abstract::In order to characterize protein targeting signals in polarized postmitotic cortical neurones in vitro, we have developed recombinant and amplicon type vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these cells. We examined the targeting of both bacterial proteins, which lack specific target...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Lowenstein PR,Bain D,Morrison EE,Preston CM,Clissold P,Fournel S,Epstein A,Castro MG

    更新日期:1994-01-01 00:00:00

  • IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice.

    abstract::Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA hu...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301274

    authors: Song K,Chang Y,Prud'homme GJ

    更新日期:2000-09-01 00:00:00

  • AAV-encoded OTC activity persisting to adulthood following delivery to newborn spf(ash) mice is insufficient to prevent shRNA-induced hyperammonaemia.

    abstract::Urea cycle defects presenting in the neonatal period with hyperammonaemia are associated with high morbidity and mortality, and necessitate liver transplantation for long-term management. Gene therapy is therefore an attractive possibility, with vectors based on adeno-associated virus (rAAV) currently showing exciting...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2013.51

    authors: Cunningham SC,Kok CY,Spinoulas A,Carpenter KH,Alexander IE

    更新日期:2013-12-01 00:00:00

  • Employment of the mdr1 promoter for the chemotherapy-inducible expression of therapeutic genes in cancer gene therapy.

    abstract::Numerous approaches in gene therapy of human cancers are focused on the establishment of cell type specific or inducible expression vectors allowing the targeted and regulated expression of therapeutic genes. Various conditionally active vectors have been created carrying promoters responding to certain factors or the...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300451

    authors: Walther W,Wendt J,Stein U

    更新日期:1997-06-01 00:00:00

  • B7H6-specific chimeric antigen receptors lead to tumor elimination and host antitumor immunity.

    abstract::Chimeric antigen receptor (CAR) T-cell therapies have demonstrated durable and potentially curative therapeutic efficacy against B-cell leukemia in clinical trials. A CAR strategy can target any tumor surface antigens as long as an antigen-binding receptor can be generated. New CARs that target solid tumors and have t...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.29

    authors: Wu MR,Zhang T,DeMars LR,Sentman CL

    更新日期:2015-08-01 00:00:00

  • A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.

    abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.48

    authors: Faitschuk E,Nagy V,Hombach AA,Abken H

    更新日期:2016-10-01 00:00:00

  • Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces B16 tumor regression through inhibition of tumor blood vessel formation monitored by Doppler ultrasonography.

    abstract::To elucidate further the potential of a Semliki Forest virus (SFV) vector in vivo for gene therapy, we constructed a vector, SFV-IL12, to transfer murine IL-12 genes into tumors. A single intratumoral injection of established B16 murine melanoma with SFV-IL12 resulted in a significant inhibition of tumor growth, while...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300841

    authors: Asselin-Paturel C,Lassau N,Guinebretière JM,Zhang J,Gay F,Bex F,Hallez S,Leclere J,Peronneau P,Mami-Chouaib F,Chouaib S

    更新日期:1999-04-01 00:00:00

  • Chitosan-plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies.

    abstract::Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.60

    authors: Jean M,Smaoui F,Lavertu M,Méthot S,Bouhdoud L,Buschmann MD,Merzouki A

    更新日期:2009-09-01 00:00:00

  • APOBEC3A catabolism of electroporated plasmid DNA in mouse muscle.

    abstract::The mouse is widely used as a model for DNA therapy and vaccination even though the efficiency of DNA delivery in higher mammals and humans is much less. The human APOBEC3 (A3) enzymes impact viral genomes by cytidine deamination, which introduces multiple uridine residues into single-stranded DNA, a process known as ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.88

    authors: Kostrzak A,Henry M,Demoyen PL,Wain-Hobson S,Vartanian JP

    更新日期:2015-01-01 00:00:00

  • Local arterial nanoparticle delivery of siRNA for NOX2 knockdown to prevent restenosis in an atherosclerotic rat model.

    abstract::Both atherosclerosis and arterial interventions induce oxidative stress mediated in part by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases that have a pivotal role in the development of neointimal hyperplasia and restenosis. For small interfering RNA (siRNA) targeting of the NOX2 (Cybb) component of the ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.69

    authors: Li JM,Newburger PE,Gounis MJ,Dargon P,Zhang X,Messina LM

    更新日期:2010-10-01 00:00:00