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Sample records for bcg live package

  1. Lively package

    International Nuclear Information System (INIS)

    Jaremko, G.

    1997-01-01

    Progress on the Lloydminster Heavy Oil Interpretive Centre, sponsored by the Lloydminster Oilfield Technical Society and expected to open in late 1998, was discussed. Some $150,000 of the $750,000 budget is already in the bank, and another $150,000 is in the pipeline. The Centre will be added to an existing and well-established visitor's site. It is reported to contain a lively and imaginatively-designed exhibit package, and promises to become a combination of educational tool and tourist attraction for the town of Lloydminster, Saskatchewan, in the heart of heavy oil country

  2. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

    Science.gov (United States)

    Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

    2017-09-01

    The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+ T cell memory immune response.

    Directory of Open Access Journals (Sweden)

    Lindsay R Ancelet

    Full Text Available Oral delivery of BCG in a lipid formulation (Liporale™-BCG targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+ T cell response, evident by the detection of effector CD4(+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.

  4. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

    Directory of Open Access Journals (Sweden)

    E M D L van der Heijden

    Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

  5. BCG Re-vaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-lived BCG-Reactive Natural Killer Cell Responses1

    Science.gov (United States)

    Suliman, Sara; Geldenhuys, Hennie; Johnson, John L.; Hughes, Jane E.; Smit, Erica; Murphy, Melissa; Toefy, Asma; Lerumo, Lesedi; Hopley, Christiaan; Pienaar, Bernadette; Chheng, Phalkun; Nemes, Elisa; Hoft, Daniel F.; Hanekom, Willem A.; Boom, W. Henry

    2016-01-01

    One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis (M.tb). We performed a phase 1 randomized, controlled trial of isoniazid preventive therapy (IPT) before re-vaccination with Bacille Calmette-Guerin (BCG) in healthy, tuberculin skin test positive (≥15mm induration), HIV-negative, South African adults. We hypothesised that pre-clearance of latent bacilli with IPT modulates BCG immunogenicity following re-vaccination. Frequencies and co-expression of IFNγ, TNFα, IL-2, IL-17, and/or IL-22 in CD4, and IFNγ-expressing CD8, γδ T, CD3+CD56+ NKT-like and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were BCG re-vaccinated after IPT (n=33) or without prior IPT (n=39). IPT had little effect on frequencies or cytokine co-expression patterns of M.tb- or BCG-specific responses. Re-vaccination transiently boosted BCG-specific Th1 cytokine-expressing CD4, CD8 and γδ T cells. Despite high frequencies of IFNγ-expressing BCG-reactive CD3+CD56+ NKT-like, CD3−CD56dim and CD3−CD56hi NK cells at baseline, BCG re-vaccination boosted these responses, which remained elevated up to one year after re-vaccination. Such BCG-reactive memory NK cells were induced by BCG vaccination in infants, while in vitro IFN-γ expression by NK cells upon BCG stimulation was dependent on IL-12 and IL-18. Our data suggest that isoniazid pre-clearance of M.tb bacilli has little effect on the magnitude, persistence or functional attributes of lymphocyte responses boosted by BCG re-vaccination. Our study highlights surprising durability of BCG-boosted memory NKT-like and NK cells expressing anti-mycobacterial effector molecules, which may be novel targets for TB vaccines. PMID:27412415

  6. Chinshan living PRA model using NUPRA software package

    International Nuclear Information System (INIS)

    Cheng, S.-K.; Lin, T.-J.

    2004-01-01

    A living probabilistic risk assessment (PRA) model has been established for Chinshan Nuclear Power Station (BWR-4, MARK-I) using NUPRA software package. The core damage frequency due to internal events, seismic events and typhoons are evaluated in this model. The methodology and results considering the recent implementation of the 5th emergency diesel generator and automatic boron injection function are presented. The dominant sequences of this PRA model are discussed, and some possible applications of this living model are proposed. (author)

  7. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice

    NARCIS (Netherlands)

    Dam, A.D. van; Bekkering, S.; Crasborn, M.; Beek, L. van der; Berg, S.M. van den; Vrieling, F.; Joosten, S.A.; Harmelen, V. van; Winther, M.P. de; Lutjohann, D.; Lutgens, E.; Boon, M.R.; Riksen, N.P.; Rensen, P.C.; Berbee, J.F.

    2016-01-01

    BACKGROUND AND AIMS: Bacille-Calmette-Guerin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on

  8. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses.

    Science.gov (United States)

    Dowling, David J; Scott, Evan A; Scheid, Annette; Bergelson, Ilana; Joshi, Sweta; Pietrasanta, Carlo; Brightman, Spencer; Sanchez-Schmitz, Guzman; Van Haren, Simon D; Ninković, Jana; Kats, Dina; Guiducci, Cristiana; de Titta, Alexandre; Bonner, Daniel K; Hirosue, Sachiko; Swartz, Melody A; Hubbell, Jeffrey A; Levy, Ofer

    2017-11-01

    Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs. Chemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo, and a range of TLR8 agonist-encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow-derived DCs enabled benchmarking of the TLR8 agonist-encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25-loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice. Although alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited T H -polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist-adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4 + T-cell numbers. TLR8 agonist

  9. BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.

    Science.gov (United States)

    Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X

    2017-06-10

    Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  11. BCG-osis after BCG vaccination in immunocompromised children: Case series and review

    Directory of Open Access Journals (Sweden)

    Soheila Shahmohammadi

    2014-02-01

    Full Text Available Bacillus Calmette Guerin (BCG developed by Albert Calmette and Camille Guerin in France between 1908 and 1921 contained a live attenuated strain of Mycobacterium bovis and was administered worldwide to prevent tuberculosis. BCG vaccination is also administered at birth to all the newborns in Iran. Disseminated BCG infection after BCG vaccination is rare. Here in, we report 2 new cases of disseminated BCGinfection and review 15 additional cases identified from our previous retrospective study during a 5-year period from 2005-2010. All of these reported patients were vaccinated. Impaired immunity was detected in 10 cases (59% including severe combined immunodeficiency, chronic granulomatous disease, Mendelian susceptibility to mycobacterial disease, combined variable immunodeficiency, and HIV infection. Response to therapy was poor among those patients with immune deficiencies, but the overall mortality rate was 32.3%. Disseminated BCG infection is a rare but devastating complication of vaccination. Immune-compromised children are at high risk of developing BCG related complications including regional BCG-itis or disseminated disease; BCG-osis.

  12. Dual Use of Packaging on the Moon: Logistics-2-Living

    Science.gov (United States)

    Howe, A. Scott; Howard, Robert

    2010-01-01

    This paper describes a modular packaging system for logistics that can be reconfigured into internal outfitting for a lunar outpost, including desks, chairs, partitions, cabinets, and radiation shielding. Logistics include clothes, equipment, food, and other consumables needed to sustain the crew for the duration of the mission. A significant mass penalty is required for the packaging and handling of logistics for re-supply of short to long-term space missions that must be brought out of the gravity well on a launch vehicle. Once the supplies have been exhausted, the packaging material is typically of no further use and is discarded. If a scheme can be developed that reuses the logistics packaging, the mass penalty can be reduced. In this research, a modular packaging system has been devised as a kit-of-parts that can be used for both handling logistics supplies, and then reconfigured into desks, chairs, partitions, cabinets, and radiation shielding. The system is derived from a standard International Space Station (ISS)-type Cargo Transfer Bag (CTB), using soft, unfoldable box-like containers with stiff metal inserts. The empty hydrogen-impregnated CTBs can be used as-is for cabinets, opened up for use as partitions, or draped over the habitat as layers of radiation shielding. Stiff metal inserts can be reconfigured into desks and other useful outfitting.

  13. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice

    NARCIS (Netherlands)

    van Dam, Andrea D.; Bekkering, Siroon; Crasborn, Malou; van Beek, Lianne; van den Berg, Susan M.; Vrieling, Frank; Joosten, Simone A.; van Harmelen, Vanessa; de Winther, Menno P. J.; Lütjohann, Dieter; Lutgens, Esther; Boon, Mariëtte R.; Riksen, Niels P.; Rensen, Patrick C. N.; Berbée, Jimmy F. P.

    2016-01-01

    Bacille-Calmette-Guérin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on cholesterol metabolism, the

  14. Tuberculosis: looking beyond BCG vaccines.

    Directory of Open Access Journals (Sweden)

    Mustafa Abu S

    2003-01-01

    Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

  15. BCG lymphadenopathy detected in a BCG-vaccinated infant

    Directory of Open Access Journals (Sweden)

    A.S. Barouni

    2004-05-01

    Full Text Available Large-scale vaccination with BCG, the live attenuated strain of Mycobacterium bovis, is being adopted around the world, although sporadic complications have occurred after the procedure. Lymphadenopathy is not uncommon especially in babies under one year (0.73% of vaccinated infants, but the swelling subsides within 2 months in most cases, with no medical or surgical treatment. Brazil adopted BCG vaccination program earlier in the seventies and by 1995 more than 96% of the infant population received this immunization. We report here the occurrence of lymphadenopathy in a two-year-old child vaccinated with the Brazilian BCG strain. The diagnosis was made using a lymph node biopsy and intestinal aspirates that yielded a positive mycobacterial culture. The isolate was resistant to isoniazid, rifampicin, pyrazinamide and thiophen-2-carbonic acid hydrazide, sensitive to streptomycin, ethambutol, and p-nitrobenzoic acid, and reacted positively to cyclo-serine and negatively to niacin. The pncA gene involved in bacterial activation of pyrazinamide contains in M. bovis a point mutation that renders pyrazinamidase unable to catalyze drug activation. Therefore, this polymorphism is a good option for developing methods to differentiate M. bovis and M. tuberculosis. Taking advantage of this difference we further analyzed the isolates by single-stranded conformation polymorphism electrophoresis of DNA following PCR of the pncA gene. The isolate identity was confirmed by RFLP electrophoretic analysis of the amplified fragment following Eco065I digestion, which selectively cleaves M. tuberculosis DNA. From this result it is proposed that RFLP of pncA gene represents an alternative for differential diagnosis of M. bovis.

  16. Package

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    Arsić Zoran

    2013-01-01

    Full Text Available It is duty of the seller to pack the goods in a manner which assures their safe arrival and enables their handling in transit and at the place of destination. The problem of packing is relevant in two main respects. First of all the buyer is in certain circumstances entitled to refuse acceptance of the goods if they are not properly packed. Second, the package is relevant to calculation of price and freight based on weight. In the case of export trade, the package should conform to the legislation in the country of destination. The impact of package on environment is regulated by environment protection regulation of Republic if Serbia.

  17. BCG: the only available vaccine against tuberculosis: review article

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    Roghayeh Teimourpour

    2017-01-01

    Full Text Available Background: Despite advances in the vaccinology and chemotherapy in the past century, tuberculosis is still responsible for two million deaths every year. Emergence of multi-drug resistant strain and coinfection of TB-HIV make it a serious concern. Treatment and control of tuberculosis is a great health burden in every community. Active tuberculosis in children has very severe consequences especially those who are under 5-years-old, therefore vaccine indication should be taken. Bacille Calmette-Guérin (BCG is a live attenuated strain of Mycobacterium bovis that has been used for providing immunity or protection against tuberculosis (TB. In addition, BCG provides relative protection against leprosy and Buruli ulcer, it also can be used for treatment of bladder cancer. BCG is the most widely administered vaccine around the world. It has been given to over three billion individuals over the past decades. At first it was developed in 1908 at the Pasteur Institute in Lille by Albert Calmette and Camille Guérin. In fact BCG is a strain of Mycobacterium bovis that bear deletion in its genome following too long subculture in special media. Deletion in region of deletion 1 (RD1, a specific region of Mycobacterium bovis genome, has decreased pathogenicity of BCG strain. Following culture of BCG on different media since 1921 make genetic variation in the BCG strains that have specific characteristics. BCG should begin given to only immune-competent individuals and should not be administered to immunocompromised people. This vaccine is not effective in people formerly infected or sensitized with environmental mycobacteria. Previous meta-analysis studies indicate that BCG has variable range of protection from 0 to 80 percent against pulmonary TB, but is very effective against severe disseminated forms such as meningitis and miliary form of TB. Despite many research and develop new generation vaccine against TB, BCG vaccine still remains as the only

  18. Mycobacterium bovis BCG vaccine induces non-specific immune responses in Japanese flounder against Nocardia seriolae.

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    Kato, Goshi; Kondo, Hidehiro; Aoki, Takashi; Hirono, Ikuo

    2012-08-01

    Nocardiosis caused by Nocardia seriolae has been causing severe loss of fish production, so that an effective vaccine is urgently needed. Mycobacterium bovis BCG (BCG) is a live attenuated vaccine for tuberculosis, which is effective against various infectious diseases including nocardiosis in mammals. In this study, the protective efficacy of BCG against N. seriolae was evaluated in Japanese flounder Paralichthys olivaceus and antigen-specific immune responses induced in BCG vaccinated fish were investigated. Cumulative mortality of BCG-vaccinated fish was 21.4% whereas that of PBS-injected fish was 56.7% in N. seriolae challenge. However, gene expression level of IFN-γ was only slightly up-regulated in BCG-vaccinated fish after injection of N. seriolae antigen. In order to reveal non-specific immune responses induced by BCG vaccination, transcriptome of the kidney after BCG vaccination was investigated using oligo DNA microarray. Gene expression levels of antimicrobial peptides such as C-type and G-type lysozyme were significantly up-regulated after BCG vaccination. Consistently, BCG vaccination appeared to increase the bacteriolysis activity of the serum against Micrococcus luteus and N. seriolae. These results suggest that BCG-vaccinated Japanese flounder fight N. seriolae infection mainly by non-specific immune responses such as by the production of bacteriolytic lysozymes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. [BCG vaccination in the world].

    Science.gov (United States)

    Toida, I

    2000-01-01

    BCG vaccination programme and BCG vaccination coverage in the world were summarized mainly based on the published informations from official organizations, such as World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Centers for Disease Control and Prevention (CDC). From this review, we can see how widely BCG has been used for the prevention of tuberculosis in the world. In most of the developing countries, especially in Africa, the Americas, and Pacific Region, BCG vaccination is carried out to newborn babies soon after birth by intradermal injection according to the recommendations from WHO, but some of the developing countries in Asia and Europe have their own modified BCG vaccination programmes. In economically developed countries, BCG vaccination programme has been established according to the tuberculosis status of each countries. Some countries have general vaccination policy, and other countries have selected vaccination policy, but there is no country where BCG vaccination is not carried out at all. Among G8 contries, as representatives of the economically developed countries, Japan, United Kingdom, France and Russian Federation have BCG general vaccination policy for the specified age group. In these 4 countries revaccination (s) of BCG are still carried out. In Germany, some provinces have general vaccination policy and some others have selected vaccination policy. In the United States of America, BCG vaccination is recommended to selected high risk infants and health care workers by CDC. There are many debates as for the efficacy and safety of BCG vaccination, and the development of new vaccine better than BCG has been actively discussed and some encouraging results in animal models have been reported from several laboratories. But, there is almost no possibility to be able to use a new vaccine in the routine practice within a couple of years. From the practical point of view, therefore, the operational

  20. IncucyteDRC: An R package for the dose response analysis of live cell imaging data

    Science.gov (United States)

    Chapman, Philip J.; James, Dominic I.; Watson, Amanda J.; Hopkins, Gemma V.; Waddell, Ian D.; Ogilvie, Donald J.

    2016-01-01

    We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web interface, implemented using shiny, is provided for the benefit of non-R users. The software is potentially useful to any research group studying the impact of small molecule inhibitors on cell proliferation using the IncuCyte ZOOM. PMID:27703665

  1. Bacillus Calmette-Guerin (BCG) Vaccine

    Science.gov (United States)

    TheraCys® BCG ... TICE® BCG ... WHY is this medicine prescribed?BCG vaccine provides immunity or protection against tuberculosis (TB). The vaccine may be given to persons at high risk of developing TB. ...

  2. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

    2015-01-01

    but not in immunocompromised hosts, as it is a live, attenuated vaccine. Therefore, we assessed whether killed γBCG has similar potentiating effects. In an in vitro model of trained immunity, human monocytes were incubated with γBCG for 24 h and restimulated after 6 d. Cytokine production and the role of pattern recognition...... were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ......BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity...

  3. Growth inhibition of HeLa cell by internalization of Mycobacterium bovis Bacillus Calmette-Guérin (BCG Tokyo

    Directory of Open Access Journals (Sweden)

    Asahina Izumi

    2009-12-01

    Full Text Available Abstract Background Intravesical BCG immunotherapy is effective for preventing recurrence and progression in none muscle-invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The mechanisms by which intravesical BCG treatment mediates antitumor activity are currently poorly understood. Results HeLa cell infected with Mycobacterium bovis Bacillus Calmette-Guérin(BCG Tokyo which were different multiplicity of infection(MOI. Proliferation of HeLa cell reduced in a dose-dependent manner by live BCG. The cytoplasm of the HeLa cell showed variety lysosomal stages by internalized and interacted BCG. Conclusion Proliferated Live BCG secreted the protein and depressed the growth of tumor. The possibility for clinical introduction of BCG therapy for carcinoma reported with review of literature.

  4. BCG-loaded chitosan microparticles: interaction with macrophages and preliminary in vivo studies.

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    Caetano, Liliana Aranha; Figueiredo, Lara; Almeida, António J; Gonçalves, L M D

    2017-03-01

    The aim of this study was to develop a novel BCG-loaded chitosan vaccine with high association efficiency which can afford efficient interaction with APC and elicit local and Th1-type-specific immune response after intranasal administration. Chitosan-suspended BCG and BCG-loaded chitosan-alginate microparticles were prepared by ionotropic gelation. Interaction with APC was evaluated by fluorescence microscopy using rBCG-GFP. Specific immune responses were evaluated following intranasal immunisation of mice. Cellular uptake was approximately two-fold higher for chitosan-suspended BCG. A single dose of BCG-loaded microparticles or chitosan-suspended BCG by intranasal route improved Th1-type response compared with subcutaneous BCG. Chitosan-suspended BCG originated the highest mucosal response in the lungs by intranasal route. These positive results indicate that the proposed approach of whole live BCG microencapsulation in chitosan-alginate for intranasal immunisation was successful in allowing efficient interaction with APC, while improving the cellular immune response, which is of interest for local immunisation against tuberculosis.

  5. Visible and subvisible particles in the BCG immunotherapeutic product Immucyst®.

    Science.gov (United States)

    Kirkitadze, Marina; Remi, Elena; Bhandal, Kamajit; Carpick, Bruce

    2016-01-01

    Bacille Calmette-Guerin, BCG, is a live attenuated bovine tubercle bacillus used for the treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT), or ImmuCyst® product using a Coulter Counter Multisizer 4® instrument. The focus of this study was to establish a baseline for reconstituted lyophilized BCG IT product using visible and sub-visible particle concentration and size distribution as reportable values. ESZ method was used to assess manufacturing process consistency using 20 production scale lots of BCG IT product. The results demonstrated that ESZ can be used to accumulate product and process knowledge of BCG IT.

  6. [Disseminated BCG infection in patients with urinary bladder carcinoma].

    Science.gov (United States)

    Korać, Milos; Milosević, Branko; Lavadinović, Lidija; Janjić, Aleksandar; Brmbolić, Branko

    2009-01-01

    Bacillus Calmette-Guërin--a live, attenuated strain of Mycobacterium bovis has been used in immunotherapy of patients with superficial urinary bladder carcinoma. Some patients develop complications after intravesical instillation of BCG: high temperature followed by hematuria or granulomatous prostatits, epidydimoorchitis, urethral obstruction, and less than 1% have a systemic disease followed by dissemination of bacteria into other organs. A 50-year-old man underwent transurethral resection of a bladder tumor. One month after the operation BCG intravesical installations were administered for three weeks. After the fourth installation, our patient developed high fever, fatigue, vomiting, dark urine, light stools, and jaundice. On admission he was jaundiced with a high fever, enlarged liver and spleen and laboratory findings which included high erythrocyte sedimentation rate, pancytopenia, elevated liver enzymes, especially alkaline phosphatase and aminotranspherases. The bone-marrow biopsy showed granulomatous inflamation suggesting mycobacterial spread in the bone marrow, liver and spleen and sepsis. The patient was initially treated with antituberculous therapy, but his state did not improve until corticosteroids were added to the antituberculous treatment regimen. Although dissemination of BCG is a rare complication of intravesical BCG treatment of the bladder carcinoma, it may result in prolonged fever and granulomatous inflamation of the liver, spleen, lungs, bone marrow and BCG sepsis. Antituberclous agents in combination with corticosteroids comprise the treatment of choice for disseminated BCG infection.

  7. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity.

    Science.gov (United States)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter; Joosten, Leo A B; de Jong, Dirk; van der Meer, Jos W M; Benn, Christine Stabell; van Crevel, Reinout; Netea, Mihai G

    2015-12-01

    BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity but not in immunocompromised hosts, as it is a live, attenuated vaccine. Therefore, we assessed whether killed γBCG has similar potentiating effects. In an in vitro model of trained immunity, human monocytes were incubated with γBCG for 24 h and restimulated after 6 d. Cytokine production and the role of pattern recognition receptors and histone methylation markers were assessed. The in vivo effects of γBCG vaccination were studied in a proof-of-principle trial in 15 healthy volunteers. γBCG induced trained immunity in vitro via the NOD2 receptor pathway and up-regulation of H3K4me3 histone methylation. However, these effects were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γBCG induces mainly heterologous effects on the adaptive-immune system, whereas effects on innate cytokine production are limited. © Society for Leukocyte Biology.

  8. Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis☆

    Science.gov (United States)

    Poyntz, Hazel C.; Stylianou, Elena; Griffiths, Kristin L.; Marsay, Leanne; Checkley, Anna M.; McShane, Helen

    2014-01-01

    Summary The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations. One possible explanation for this variability is increased exposure of certain populations to non-tuberculous mycobacteria (NTM). This study used a murine model to determine the effect that exposure to NTM after BCG vaccination had on the efficacy of BCG against aerosol Mycobacterium tuberculosis challenge. The effects of administering live Mycobacterium avium (MA) by an oral route and killed MA by a systemic route on BCG-induced protection were evaluated. CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy. BCG efficacy was enhanced by exposure to killed MA administered by a systemic route; T helper 1 and T helper 17 responses were associated with increased protection. BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection. These findings demonstrate that exposure to NTM can induce opposite effects on BCG efficacy depending on route of exposure and viability of NTM. A reproducible model of NTM exposure would be valuable in the evaluation of novel TB vaccine candidates. PMID:24572168

  9. Ultrasonographic features of BCG lymphadenitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Youn; Lee, Sun Wha; Hwang, Ji Young [College of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

    2005-07-15

    To evaluate the ultrasonographic findings of BCG lymphadenitis complicated by BCG vaccination in children. Ultrasonography was performed for 22 cases of BCG lymphadenitis in 21 patients who were diagnosed by clinical (n=10) or pathological (n=11) examinations. Their age ranged from 4 months to 3 years (mean age; 14 months). We retrospectively analyzed the ultrasonographic findings for location, multiplicity, size, shape, margin, echogenecity, posterior enhancement, calcifications, inner anechoic portion and Doppler pattern of the BCG lymphadenitis. The BCG lymphadenitis was found at the axillary area in 15 cases (68%) and at the supraclavicular area in 7 cases (32%). There were ten cases (45%) of solitary lesion and 12 cases (55%) of multiple conglomerated lesions. The maximum diameter ranged from about 0.9 cm to 3.2 cm. The BCG lymphadenitis showed as round (82%), well defined (86%), or heterogeneous hypoechoic (68%) lesions with posterior enhancement (78%). Calcifications were found in 6 cases (27%) and 5 cases (83%) had been vaccinated more than 5 months ago. There were eccentric inner anechoic portions in 16 cases (73%), which were pathologically confirmed as having caseating necrosis. There were increased Doppler flow patterns in 15 cases (68%); 4 cases (18%) were of the central type, 6 cases (27%) were of the peripheral type and 5 cases (23%) were of mixed type. BCG lymphadenitis is frequently located at the axillary area adjacent to a vaccination site. The ultrasonographic findings of BCG lymphadenitis are well-defined, round, heterogeneously hypoechoic lesions with posterior enhancement, calcifications and inner eccentric anechoic portion.

  10. Ultrasonographic features of BCG lymphadenitis

    International Nuclear Information System (INIS)

    Kim, Do Youn; Lee, Sun Wha; Hwang, Ji Young

    2005-01-01

    To evaluate the ultrasonographic findings of BCG lymphadenitis complicated by BCG vaccination in children. Ultrasonography was performed for 22 cases of BCG lymphadenitis in 21 patients who were diagnosed by clinical (n=10) or pathological (n=11) examinations. Their age ranged from 4 months to 3 years (mean age; 14 months). We retrospectively analyzed the ultrasonographic findings for location, multiplicity, size, shape, margin, echogenecity, posterior enhancement, calcifications, inner anechoic portion and Doppler pattern of the BCG lymphadenitis. The BCG lymphadenitis was found at the axillary area in 15 cases (68%) and at the supraclavicular area in 7 cases (32%). There were ten cases (45%) of solitary lesion and 12 cases (55%) of multiple conglomerated lesions. The maximum diameter ranged from about 0.9 cm to 3.2 cm. The BCG lymphadenitis showed as round (82%), well defined (86%), or heterogeneous hypoechoic (68%) lesions with posterior enhancement (78%). Calcifications were found in 6 cases (27%) and 5 cases (83%) had been vaccinated more than 5 months ago. There were eccentric inner anechoic portions in 16 cases (73%), which were pathologically confirmed as having caseating necrosis. There were increased Doppler flow patterns in 15 cases (68%); 4 cases (18%) were of the central type, 6 cases (27%) were of the peripheral type and 5 cases (23%) were of mixed type. BCG lymphadenitis is frequently located at the axillary area adjacent to a vaccination site. The ultrasonographic findings of BCG lymphadenitis are well-defined, round, heterogeneously hypoechoic lesions with posterior enhancement, calcifications and inner eccentric anechoic portion

  11. Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle.

    Science.gov (United States)

    Villarreal-Ramos, Bernardo; Berg, Stefan; Chamberlain, Laura; McShane, Helen; Hewinson, R Glyn; Clifford, Derek; Vordermeier, Martin

    2014-09-29

    Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  12. Loss of BCG Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to BCG Exposure

    Science.gov (United States)

    Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, YanLi; Kalyanaraman, Balaraman; See, William

    2018-01-01

    INTRODUCTION The attenuated mycobacterium Bacille Calmette Guerin (BCG) is widely utilized as intravesical “immunotherapy” for the treatment of non-muscle invasive urothelial carcinoma. Previous studies have demonstrated that in both the laboratory and clinical setting, BCG viability is a variable that correlates with anti-tumor efficacy. This study evaluated how loss of BCG viability impacted a number of molecular and phenotypic intermediate endpoints that characterize, and/or contribute to, the direct effect of BCG on Urothelial carcinoma (UC) cells. MATERIALS AND METHODS Two human UC cell lines were used to study the effect of loss of BCG viability on the tumor cell response to BCG. The cellular response to BCG rendered non-viable by heat killing (hk) was compared to the response to viable BCG. The response endpoints evaluated included the induction of oxidative stress, activation of intracellular signaling pathways, gene transactivation, and phenotypic changes. RESULTS Loss of viability resulted in a quantitative decrease in the tumor cell response, relative to viable BCG, for all of the measured endpoints. The decrease in response varied by cell line, ranging from 15% to 100% of the response to viable BCG. While quantitatively different, non-viable BCG continued to induce responses that were qualitatively similar to BCG relative to untreated controls. CONCLUSIONS BCG viability is an important variable influencing the direct tumor cell response to BCG. Although the magnitude of it effects are attenuated, hkBCG remains active for the induction of BCG responsive biologic endpoints. PMID:24035882

  13. Systemic BCG-osis following intravesical BCG instillation for bladder carcinoma.

    Science.gov (United States)

    Liaw, Frank; Tan, Yan Yu; Hendry, David

    2017-10-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) has been shown to be an effective form of immunotherapy for bladder cancer. This case report describes a patient who develops systemic BCG-osis following intravesical BCG instillation and demonstrates the importance of being aware of more severe complications associated with BCG immunotherapy.

  14. Lupus Vulgaris Following Bcg Vaccination

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    R K Pandhi

    1982-01-01

    Full Text Available Three cases of lupus vulgaris developing at the site of BCG vaccination are reported. All the patients had lesions starting before the age of 15 years. Clinically and histologically the lesions ′were indistinguishable from spontaneous lupus vulgarism Treatment with streptomycin and isonicotinic acid hydrazide for 1 year produced complete resolution of lesions.

  15. Mycotic aortic aneurysm due to intravesical BCG immunotherapy: Clinical manifestations and diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Brittany J Holmes

    2014-01-01

    Full Text Available A live, attenuated form of Mycobacterium bovis, bacillus Calmette–Guérin (BCG, is commonly used as intravesical immunotherapy for non-invasive urothelial bladder carcinoma. While complications are rare, dissemination can occur. A case of mycotic aortic aneurysm following BCG administration with recovery of Mycobacterium bovis in culture is reported. A review of the published experience with this problem is also presented.

  16. Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant

    Directory of Open Access Journals (Sweden)

    Böttger Erik C

    2008-07-01

    Full Text Available Abstract Background The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. Results As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia. Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA. Conclusion According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type.

  17. Evolution and Strain Variation in BCG

    KAUST Repository

    Abdallah, Abdallah

    2017-11-07

    BCG vaccines were derived by in vitro passage, during the years 1908–1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.

  18. Evolution and Strain Variation in BCG.

    Science.gov (United States)

    Abdallah, Abdallah M; Behr, Marcel A

    2017-01-01

    BCG vaccines were derived by in vitro passage, during the years 1908-1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.

  19. The patterns of in vitro cell-death and inflammatory cytokines induced by distinct BCG vaccine strains are differentially induced in human mononuclear cells.

    Science.gov (United States)

    Ponte, C; Hacker, M; Moraes, M; Castello-Branco, L; Silva, F; Antas, P

    2018-01-02

    Tuberculosis (TB) remains among the world's leading cause of mortality. For its control, studies of TB vaccines are needed. Since live-attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only TB vaccine currently in use, studies on the protective role of BCG are required. In this study, we analyzed host cells purified directly from whole blood of human immunodeficiency virus (HIV)-negative volunteers, comprising adult healthy donors (HD) and neonates (umbilical cord bloods, UCB), with the aim to directly compare in vitro immune responses with distinct BCG strains in human mononuclear cells. The Moreau, Pasteur, and Danish BCG strains were used to infect mononuclear cells in vitro for 48 h; bacilli viability and cell-death were subsequently detected by flow cytometry. In addition, cell culture supernatants were used in cytokine detection assays. Overall, the Moreau BCG strain induced higher levels of apoptosis than the Pasteur and Danish BCG strains in both the HD and UCB groups (p-value BCG infection. The Moreau BCG strain, exclusively, induced Th1 cytokines at the highest levels in cells from adults (p-value BCG strains, whereas TGF-β1 levels were reduced significantly (p-value BCG vaccine. As expected, eight out of 22 pro-inflammatory cytokines were secreted at significant levels (p-value BCG-infected cell cultures, in the HD group only. When analyzing these results, we excluded confounding factors related to storage and viability of the BCG strains used. These findings suggest that Moreau BCG is a more potent immunostimulating agent than the Pasteur and Danish BCG strains. Clinical trials will be needed to confirm these findings.

  20. Improvement of Thermal Stability of BCG Vaccine

    Science.gov (United States)

    Jahanbakhsh Sefidi, Fatemeh; Kaghazian, Homan; Moradli, Gholam Ali; Hassanzadeh, Seyed Mehdi

    2017-11-01

    Thermal stability (TS) is a part of the BCG vaccine characterization by which the consistency of process in BCG vaccine production could be confirmed. To enhance the TS of the vaccine, some prevalent stabilizers in different concentrations were added to the final formulation of BCG bulk prior to Freeze-drying process. We found a formulation more effective than the current stabilizer for retaining the higher viability of lyophilized BCG vaccine produced by Pasteur Institute of Iran. In the design of experiments using Taguchi method, lactose, trehalose, glucose, dextran, and monosodium glutamate were added to the final formulation of BCG bulk prior to freeze-drying process. Viability of the samples was determined by counting the colony forming unit. Maximum signal-to-noise ratio equal to maximum TS and viability was obtained by adding lactose, dextran, and glutamate in defined concentrations. Adding the stabilizers had a significant impact on TS of BCG vaccine to meet the quality requirements.

  1. Tuberculous spondylitis following BCG vaccination

    International Nuclear Information System (INIS)

    Mueller-Miny, H.; Bick, U.; Lengerke, H.J. von; Ritter, J.; Reiser, M.

    1990-01-01

    A case of a rare form of BCG osteomyelitis in the spine is presented. After vaccination, the disease started with a lymphadenitis. Later an abscess extended from the pelvic along the psoas muscles into the retroperitoneum. The soft tissue mass extended paraspinally and epidural involvement was also apparent. The vertebral involvement was detected by CT. The radiological findings are discussed with reference to the literature. (orig.)

  2. Tuberculin reaction and BCG scar

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter

    2015-01-01

    rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW...

  3. Health-Care Associated Mycobacterium bovis-BCG Infection in Cancer Patients without prior BCG Instillation.

    Science.gov (United States)

    Meije, Y; Martínez-Montauti, J; Caylà, J A; Loureiro, J; Ortega, L; Clemente, M; Sanz, X; Ricart, M; Santomà, M J; Coll, P; Sierra, M; Calsina, M; Vaqué, M; Ruiz-Camps, I; López-Sánchez, C; Montes, M; Ayestarán, A; Carratalà, J; Orcau, A

    2017-05-29

    Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is widely used as adjunctive therapy for superficial bladder cancer. Intravesical administration of BCG has been associated with systemic infection. Disseminated infection due to M. bovis is otherwise uncommon. After identification of three patients with health-care associated BCG infection (HCBCGI) who had never received intravesical BCG administration, an epidemiologic study was performed. All patients with HCBCGI in the Barcelona tuberculosis (TB) program were reviewed from January 1, 2005 to December 31, 2015 searching for infections caused by M. bovis-BCG. Patients with HCBCGI who had not received intravesical BCG instillation were selected and the source of infection was investigated. Nine oncology patients with infection caused by M. bovis-BCG were studied. All had permanent central venous catheters. Catheter maintenance was performed at four different outpatient clinics in the same room in which other patients underwent BCG instillations for bladder cancer without required biological precautions. All patients developed pulmonary TB, either alone or with extrapulmonary disease. Catheter-related infection was considered the mechanism of acquisition based on the epidemiologic association and positive catheter cultures for BCG in patients in whom mycobacterial cultures were performed. Physicians should be alerted to the possibility of TB due to nosocomially acquired, catheter-related infections with M. bovis-BCG in patients with indwelling catheters. This problem may be more common than expected in centers providing BCG therapy for bladder cancer without adequate precautions.

  4. BCG coverage and barriers to BCG vaccination in Guinea-Bissau

    DEFF Research Database (Denmark)

    Thysen, Sanne Marie; Byberg, Stine; Pedersen, Marie

    2014-01-01

    BACKGROUND: BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination ("restricted vial-opening policy"). BCG coverage is usually reported as 12-month coverage......, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau. METHODS: Bandim Health Project (BHP) runs a health and demographic surveillance system...... in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios. RESULTS: Among 3951 children born in 2010...

  5. Disseminated Bacillus Calmette-Guérin (BCG) infections in infants with immunodeficiency.

    Science.gov (United States)

    Al-Hammadi, Suleiman; Alsuwaidi, Ahmed R; Alshamsi, Eman T; Ghatasheh, Ghassan A; Souid, Abdul-Kader

    2017-05-05

    The Bacillus Calmette-Guérin (BCG) preparations are live-attenuated derivatives of Mycobacterium bovis. These products are used to vaccinate infants at birth, a practice that may result in a disseminated infection in those patients who have an unidentified immunodeficiency. Patients who were immunized at birth with BCG and who developed a disseminated infection are reported here to emphasize the importance of taking an extensive medical history before ‎giving the BCG vaccine. Patient 1 has a sibling who had familial hemophagocytic lymphohistiocytosis. Patient 2 has a severe immunodeficiency with profound lymphopenia. Patient 3 has a sibling who had a disseminated BCG infection. Patient 4 has two siblings with an immunodeficiency disorder; one sibling passed away in infancy and one is receiving regular immunoglobulin infusions. Patient 5 has profound lymphopenia and his brother had cytomegalovirus (CMV) pneumonitis and passed away in infancy. These unfortunate events could have been avoided by compiling the relevant clinical and laboratory information. These cases also underscore the importance of a strict adherence to the BCG vaccine policies. Local and international registries that estimate the birth prevalence of primary immune deficiencies are needed prior to implementing universal BCG vaccination administration.

  6. Tuberculin Reaction Among Healthy BCG Vaccinated Primary ...

    African Journals Online (AJOL)

    Objective: To assess the Mantoux test reaction pattern in healthy BCG vaccinated Primary School Children aged 6 -10 years in Nnewi, South–East Nigeria. Materials and methods:Four Primary Schools were randomly selected out of 43 government owned primary schools in the town. The entire BCG vaccinated pupils in ...

  7. Recombinant BCG Expressing Mycobacterium ulcerans Ag85A Imparts Enhanced Protection against Experimental Buruli ulcer.

    Science.gov (United States)

    Hart, Bryan E; Hale, Laura P; Lee, Sunhee

    2015-09-01

    Buruli ulcer, an emerging tropical disease caused by Mycobacterium ulcerans (MU), is characterized by disfiguring skin necrosis and high morbidity. Relatively little is understood about the mode of transmission, pathogenesis, or host immune responses to MU infection. Due to significant reduction in quality of life for patients with extensive tissue scarring, and that a disproportionately high percentage of those affected are disadvantaged children, a Buruli ulcer vaccine would be greatly beneficial to the worldwide community. Previous studies have shown that mice inoculated with either M. bovis bacille Calmette-Guérin (BCG) or a DNA vaccine encoding the M. ulcerans mycolyl transferase, Ag85A (MU-Ag85A), are transiently protected against pathology caused by intradermal challenge with MU. Building upon this principle, we have generated quality-controlled, live-recombinant strains of BCG and M. smegmatis which express the immunodominant MU Ag85A. Priming with rBCG MU-Ag85A followed by an M. smegmatis MU-Ag85A boost strongly induced murine antigen-specific CD4+ T cells and elicited functional IFNγ-producing splenocytes which recognized MU-Ag85A peptide and whole M. ulcerans better than a BCG prime-boost vaccination. Strikingly, mice vaccinated with a single subcutaneous dose of BCG MU-Ag85A or prime-boost displayed significantly enhanced survival, reduced tissue pathology, and lower bacterial load compared to mice vaccinated with BCG. Importantly, this level of superior protection against experimental Buruli ulcer compared to BCG has not previously been achieved. These results suggest that use of BCG as a recombinant vehicle expressing MU antigens represents an effective Buruli ulcer vaccine strategy and warrants further antigen discovery to improve vaccine efficacy.

  8. Recombinant BCG Expressing Mycobacterium ulcerans Ag85A Imparts Enhanced Protection against Experimental Buruli ulcer

    Science.gov (United States)

    Hart, Bryan E.; Hale, Laura P.; Lee, Sunhee

    2015-01-01

    Buruli ulcer, an emerging tropical disease caused by Mycobacterium ulcerans (MU), is characterized by disfiguring skin necrosis and high morbidity. Relatively little is understood about the mode of transmission, pathogenesis, or host immune responses to MU infection. Due to significant reduction in quality of life for patients with extensive tissue scarring, and that a disproportionately high percentage of those affected are disadvantaged children, a Buruli ulcer vaccine would be greatly beneficial to the worldwide community. Previous studies have shown that mice inoculated with either M. bovis bacille Calmette–Guérin (BCG) or a DNA vaccine encoding the M. ulcerans mycolyl transferase, Ag85A (MU-Ag85A), are transiently protected against pathology caused by intradermal challenge with MU. Building upon this principle, we have generated quality-controlled, live-recombinant strains of BCG and M. smegmatis which express the immunodominant MU Ag85A. Priming with rBCG MU-Ag85A followed by an M. smegmatis MU-Ag85A boost strongly induced murine antigen-specific CD4+ T cells and elicited functional IFNγ-producing splenocytes which recognized MU-Ag85A peptide and whole M. ulcerans better than a BCG prime-boost vaccination. Strikingly, mice vaccinated with a single subcutaneous dose of BCG MU-Ag85A or prime-boost displayed significantly enhanced survival, reduced tissue pathology, and lower bacterial load compared to mice vaccinated with BCG. Importantly, this level of superior protection against experimental Buruli ulcer compared to BCG has not previously been achieved. These results suggest that use of BCG as a recombinant vehicle expressing MU antigens represents an effective Buruli ulcer vaccine strategy and warrants further antigen discovery to improve vaccine efficacy. PMID:26393347

  9. Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jiangan Xie

    Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

  10. Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis

    Science.gov (United States)

    Xie, Jiangan; Codd, Christopher; Mo, Kevin; He, Yongqun

    2016-01-01

    M. bovis strain Bacillus Calmette–Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE)-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis), skin (e.g., skin ulceration and cyanosis), and respiratory system (e.g., cough and pneumonia); in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria). With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased) shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG-associated death

  11. BCG status in children with tuberculosis: A multicenter study in ...

    African Journals Online (AJOL)

    Background: Bacille Calmette.Guerin (BCG) vaccine has been in use since 1921, yet childhood TB is still very prevalent in Nigeria. Since BCG efficacy depends in part on appropriate vaccine utilization, this study was designed to investigate the current practice of BCG administration through determination of BCG status.

  12. [Disseminated BCG infection revealing X-linked severe combined immunodeficiency].

    Science.gov (United States)

    Marchand, I; Mahé, E; Clérici, T; Saiag, P; Chevallier, B

    2008-01-01

    Live attenuated Bacillus Calmette-Guérin (BCG) vaccine is rarely responsible for disseminated infection. We report a case of X-linked severe combined immunodeficiency (SCID) revealed by a disseminated skin infection. A 4-month-old baby was hospitalized for prolonged gastroenteritis. He was in poor general condition, with prolonged fever, oral and gluteal candidiasis and purple nodules associated with ulceration of the BCG scar. The absence of a thymus, T-cells and NK-cells, and the presence of nonfunctional B-lymphocytes led to a diagnosis of SCID. Biopsies of nodules revealed a dermal infiltrate without necrosis. A Ziehl-Neelson stain was highly positive and the culture grew Mycobacterium bovis. Treatment consisted of a four-drug antibiotic regimen directed against M. bovis combined with gamma interferon, immunoglobulins and antibiotic prophylaxis by cotrimoxazole and was followed by a haploid-identical bone marrow transplant without rejection at six months. The early death of the child's maternal uncle from sepsis suggested X-linked transmission, which was subsequently confirmed by genetic analysis. BCG vaccination can cause serious infections in immunocompromised subjects. Skin involvement is extremely rare but may be the first sign of SCID, of which the X-linked form is the most common and corresponds to a variety of mutations in the gene coding for the gamma chain common to several interleukin receptors. Genetic counselling is essential to identify female carriers and allow early antenatal diagnosis. Bone marrow transplantation is the only treatment.

  13. Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma

    International Nuclear Information System (INIS)

    Larsson, S.-E.; Lorentzon, R.; Boquist, L.

    1981-01-01

    The effects of immunotherapy with irradiated tumour cells and BCG were studied in a non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 x 10 6 irradiated tumour cells each 1 to 3 weeks before administration of 1 x 10 6 living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P<0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-weeks intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast o the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere. (author)

  14. Evaluation of spoilage potential and volatile metabolites production by Shewanella baltica isolated from modified atmosphere packaged live mussels.

    Science.gov (United States)

    Odeyemi, Olumide A; Burke, Christopher M; Bolch, Christopher J S; Stanley, Roger

    2018-01-01

    Under the current commercial practice, live mussels only have 10days' shelf-life. Observed spoilage indices reduce consumers' acceptance, palatability and shelf-life of modified atmosphere packaged (MAP) live mussels. The aims of this study are to isolate specific spoilage bacteria from modified atmosphere packaged live mussels, evaluate isolates for microbial spoilage indices using qualitative methods and volatile metabolites production. Forty-six hydrogen sulphide producing bacteria were isolated and evaluated for trimethylamine n-oxide (TMAO) reduction, proteolytic and lipolytic activities and hydrogen sulphide production. Twenty-eight isolates were obtained from pouch water and 18 from mussel meat. All the isolates could produce H 2 S on Iron agar at 25°C while 30/46 produced H 2 S at 4°C and tolerate 0-6% NaCl. Four (4/46) isolates could not hydrolyse mussel protein. Over 80% isolates reduced TMAO to TMA in 3days with the production of H 2 S. Results of this study shows hydrogen sulphide producing bacteria isolated from MAP live mussels produce microbial spoilage indices. Isolate with highest enzymatic activities and hydrogen sulphide production was identified as Shewanella baltica using 16S rRNA gene. Axenic culture of the isolate was inoculated into sterile mussel broth. Inoculated sample was further stored at 4°C for 10days for spoilage study. Volatile metabolites produced during storage were evaluated using headspace solid phase micro-extraction gas chromatography mass spectrometry (HS-SPME GC/MS). A total of 44 compounds were identified in the sample after 10days while 27 compounds were identified in inoculated mussel broth. Group of compounds identified are alcohols, aldehydes, phenol, furans, ketone, esters, organic acid, aromatic hydrocarbons, alkanes, nitrogen and sulphur containing compounds. Dimethyl trisulphide, methyl-phenol, 3,5-octadiene and thiohexene were unique to inoculated mussel broth. Understanding spoilage mechanism and attendant

  15. Bladder Cancer Immunotherapy: BCG and Beyond

    Directory of Open Access Journals (Sweden)

    Eric J. Askeland

    2012-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette-Guérin (BCG has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1 immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  16. Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

    Directory of Open Access Journals (Sweden)

    M. J. Pereira Filho

    1955-12-01

    the repetition of the tests, even though the intensity of the reaction always remains the same. This precocious reaction (Fernandez type occurs both shortly and long time after the application of the BCG. Its precocity depends not of the antigen only because the first Mitsuda's reaction after the BCG application occurs after some time and seems not influenced by the control lepromin test effected on the Rhesus before the BCG. 5 On the control group, the animals which received a.a.f. bacilli suspensions (Mycobacterium sp.; M. avium, and M. smegmatis, did not show reverseals of the Mitsuda's reaction. Two Rhesus, however, which received dead BCG (120ºC autoclave 1 hour, one intradermically (0.006 g and the other orally (1.2 g, did both present reversals of the Mitsuda's reaction, with weak positivity (+. In all animals of the control-group, the allergic reactions were found negative. 6 Strong local inflammatory reactions were observed in the Rhesus that had received living BCG by intradermal via, and in the one submitted to multipunctures, there occurred the formation of a large caseous abcess. 7 The allergic tuberculinic and infratuberculinic reactions appeared dissociated from the Mitsuda's reactions: sometimes they are more precocious, occurring before of the lepromin test; on other occasions they disappear, when the Mitsuda's reactions still persist; and finally, they may be absent, when the latter occur, especially after the oral application of the BCG. 8 In Rhesus which received BCG by testicular and peritonela via, in the infratuberculinic test (0.1 ml of total BCG extract, besides the classic answer, which occurs between 48 and 96 hours, one could observe a delayed answer (15 to 20 days, represented by a non-erythematous nodule, which persists for 11-14 days.

  17. The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperendemic shanty-town, Peru

    Science.gov (United States)

    Saito, M.; Bautista, C. T.; Gilman, R. H.; Bowering, A.; Levy, M. Z.; Evans, C. A.

    2010-01-01

    SUMMARY SETTING The tuberculin skin test (TST) is widely used as a diagnostic or screening test for Mycobacterium tuberculosis infection and disease. A peri-urban shanty-town in the desert hills of south Lima, Peru, highly endemic for tuberculosis, and where bacille Calmette-Guérin (BCG) vaccine had been given in multiple doses until 1995. OBJECTIVE To analyze the effect of multiple BCG vaccines on TST in a community-based setting. DESIGN Point-prevalence survey of TST reactions of 572 people aged 6–26 years from 255 households. TST reactions were compared to the observed number of BCG scars and other potential risk factors (age, living with a TST-positive person, and contact with active tuberculosis). RESULT People with two or more scars had significantly larger reactions, even after adjusting for potential risk factors. The adjusted population attributable fraction of being TST-positive and having two or more BCG scars was 26%. CONCLUSION There is no demonstrated benefit of repeat BCG vaccination. We therefore recommend that physicians take into consideration the number of BCG scars when interpreting the TST and that programs give no more than one BCG vaccination. PMID:15260275

  18. The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo.

    Science.gov (United States)

    Pedroza-Roldán, César; Guapillo, Carolina; Barrios-Payán, Jorge; Mata-Espinosa, Dulce; Aceves-Sánchez, Michel de Jesús; Marquina-Castillo, Brenda; Hernández-Pando, Rogelio; Flores-Valdez, Mario Alberto

    2016-09-14

    Mycobacterium tuberculosis (Mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (TB). Until today, the only licensed vaccine against Mtb is the live attenuated M. bovis Bacillus Calmette-Guérin (BCG), which has variable levels of protection against the pulmonary form of infection. The quest for a new vaccine is a priority given the rise of multidrug-resistant Mtb around the world, as well as the tremendous burden imposed by latent TB. The objective of this study was to evaluate the immunogenicity and capacity of protection of a modified BCG strain (BCGΔBCG1419c) lacking the c-di-GMP phosphodiesterase gene BCG1419c, in diverse mice models. In a previous report, we have shown that BCGΔBCG1419c was capable of increasing biofilm production and after intravenous infection of immunocompetent mice; this strain persisted longer in lungs than parental BCG Pasteur. This led us to hypothesize that BCGΔBCG1419c might therefore possess some advantage as vaccine candidate. Our results in this report indicate that compared to conventional BCG, vaccination with BCGΔBCG1419c induced a better activation of specific T-lymphocytes population, was equally effective in preventing weight loss despite being used at lower dose, reduced tissue damage (pneumonic scores), increased local IFNγ(+) T cells, and diminished bacterial burden in lungs of BALB/c mice infected intratracheally with high dose Mtb H37Rv to induce progressive TB. Moreover, vaccination with BCGΔBCG1419c improved resistance to reactivation after immunosuppression induced by corticosterone in a murine model of chronic infection similar to latent TB. Furthermore, despite showing increased persistence in immunocompetent mice, BCGΔBCG1419c was as attenuated as parental BCG in nude mice. To our knowledge, this is the first demonstration that a modified BCG vaccine candidate with increased pellicle/biofilm production has the capacity to protect against Mtb challenge in

  19. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice.

    Science.gov (United States)

    van Dam, Andrea D; Bekkering, Siroon; Crasborn, Malou; van Beek, Lianne; van den Berg, Susan M; Vrieling, Frank; Joosten, Simone A; van Harmelen, Vanessa; de Winther, Menno P J; Lütjohann, Dieter; Lutgens, Esther; Boon, Mariëtte R; Riksen, Niels P; Rensen, Patrick C N; Berbée, Jimmy F P

    2016-08-01

    Bacille-Calmette-Guérin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on cholesterol metabolism, the main driver of atherosclerosis development, has remained underexposed in previous studies. Therefore, we aimed to elucidate the effect of BCG on cholesterol metabolism in addition to inflammation and atherosclerosis development in APOE*3-Leiden.CETP mice, a well-established model of human-like lipoprotein metabolism. Hyperlipidemic APOE*3-Leiden.CETP mice were fed a Western-type diet containing 0.1% cholesterol and were terminated 6 weeks after a single intravenous injection with BCG (0.75 mg; 5 × 10(6) CFU). BCG-treated mice exhibited hepatic mycobacterial infection and hepatomegaly. The enlarged liver (+53%, p = 0.001) coincided with severe immune cell infiltration and a higher cholesterol content (+31%, p = 0.03). Moreover, BCG reduced plasma total cholesterol levels (-34%, p = 0.003), which was confined to reduced nonHDL-cholesterol levels (-36%, p = 0.002). This was due to accelerated plasma clearance of cholesterol from intravenously injected [(14)C]cholesteryl oleate-labelled VLDL-like particles (t½ -41%, p = 0.002) as a result of elevated hepatic uptake (+25%, p = 0.05) as well as reduced intestinal cholestanol and plant sterol absorption (up to -37%, p = 0.003). Ultimately, BCG decreased foam cell formation of peritoneal macrophages (-18%, p = 0.02) and delayed atherosclerotic lesion progression in the aortic root of the heart. BCG tended to decrease atherosclerotic lesion area (-59%, p = 0.08) and reduced lesion severity. BCG reduces plasma nonHDL-cholesterol levels and delays atherosclerotic lesion formation in hyperlipidemic mice. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  20. Recombinant BCG: Innovations on an old vaccine. Scope of BCG strains and strategies to improve long lasting memory

    Directory of Open Access Journals (Sweden)

    Adeliane C da Costa

    2014-04-01

    Full Text Available BCG (Bacille Calmette-Guérin, an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB. Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort towards the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words tuberculosis, rBCG vaccine and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of M. tuberculosis (Mtb immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and over expression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC::hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory.

  1. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

    NARCIS (Netherlands)

    Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

    2017-01-01

    Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

  2. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    Directory of Open Access Journals (Sweden)

    Degrave Wim M

    2011-04-01

    Full Text Available Abstract Background Bacille Calmette-Guerin (BCG is currently the only available vaccine against tuberculosis (TB and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa, Rv1926c (BCG1965c, Mpb63 and Rv1886c (BCG1923c, Ag85B in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2 and Rv0350 (BCG0389, DnaK, show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

  3. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur.

    Science.gov (United States)

    Berrêdo-Pinho, Marcia; Kalume, Dario E; Correa, Paloma R; Gomes, Leonardo H F; Pereira, Melissa P; da Silva, Renata F; Castello-Branco, Luiz R R; Degrave, Wim M; Mendonça-Lima, Leila

    2011-04-20

    Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3-8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern. Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

  4. Original Article Failure of Bacillus Calmette Guerin (BCG) Therapy ...

    African Journals Online (AJOL)

    Administrator

    -up, 6 (3.8%) stopped BCG due to side-effects and were subsequently treated with intravesical chemotherapy, while another 5 (3.1%) died during BCG therapy ... patients with impaired renal function. Hematuria was the most common clinical.

  5. BCG and Kawasaki disease in Mexico and Japan.

    Science.gov (United States)

    Gamez-Gonzalez, Luisa Berenise; Hamada, Hiromichi; Llamas-Guillen, Beatriz Adriana; Ruiz-Fernandez, Miguel; Yamazaki-Nakashimada, Marco

    2017-05-04

    Dr. Tomisaku Kawasaki was the first to describe BCG reactivation in Kawasaki Disease (K D ), and this sign is present in about 30-50% of K D patients. It is a very specific early sign of the disease and although it has been recognized for decades, its pathophysiology continues to be an enigma. Recently, Yamada et al. reported a severe BCG reaction with tuberculid in 2 Japanese K D patients. We present 2 cases with K D and severe BCG reaction, one from Japan and the other from Mexico and review the policies of administration of BCG in both countries. The BCG vaccine has a worldwide coverage of 88%. Differences in BCG strains and methods of administration may influence BCG reactions in K D . The BCG reaction in the inoculation site may represent the most useful sign in K D .

  6. The second Geneva Consensus: Recommendations for novel live TB vaccines.

    Science.gov (United States)

    Walker, K B; Brennan, M J; Ho, M M; Eskola, J; Thiry, G; Sadoff, J; Dobbelaer, R; Grode, L; Liu, M A; Fruth, U; Lambert, P H

    2010-03-08

    Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including: i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype. ii. To identify the general criteria for further clinical development from Phase I through to Phase III. iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held. iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine. v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme. Copyright 2010. Published by Elsevier

  7. Effectiveness of BCG vaccination to aged mice

    Directory of Open Access Journals (Sweden)

    Ito Tsukasa

    2010-09-01

    Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

  8. Children with lymphadenitis associated with Bacillus Calmette-Guérin (BCG) vaccination do not experience more infections when compared with BCG-vaccinated children without lymphadenitis: a three years paired-cohort in Mexico.

    Science.gov (United States)

    Chacon-Cruz, Enrique; Arellano-Estrada, Jorge Luis; Lopatynsky-Reyes, Erika; Alvelais-Palacios, Jorge; Becka, Chandra

    2017-08-01

    Vaccination against tuberculosis with live-attenuated Bacillus Calmette-Guérin (BCG) is widely used even though its effectiveness is controversial. BCG-lymphadenitis (BCG-LA) is its most common complication. Some studies have proposed that BCG-LA can be associated with primary immunodeficiencies (PIs). This study's aim is to see whether patients who developed BCG-LA (named as 'LA') developed more infections than BCG-vaccinated children without BCG-LA (named as 'NON-LA'). From January 2009 to April 2014, 31 LA children were seen at the outpatient clinic of the General Hospital of Tijuana, Mexico. Among them, 22 (70.97%), 5 (16.13%) and 4 (12.9%) had axillary, supraclavicular, or both BCG-LA, respectively. No treatment was given and complications were not seen. Per LA subject, a NON-LA not >1 month of age difference and same gender was paired and followed for 3 years to look for ambulatory infections (AINFs), acute otitis media (AOM) and hospitalizations. Surveillance per patient was performed by phone monthly, and they were seen at the clinic every 4 months. All patients were HIV-negative and had no family history of PI. Statistical analyses used were relative risk (RR) with confidence intervals (CI), t test for independent variables and z test. In total 62 subjects were enrolled: 31 LA paired with 31 NON-LA. Between them, there were no differences in age, day care attendance and breastfeeding. There were no differences in the total number of AINF per patient (LA: 18.61 avg. ± 5.03 SD versus NON-LA: 18.19 avg. ± 4.17 SD, RR = 1.06, 95% CI = 0.33-0.66), AOM total episodes (LA: 30 versus NON-LA: 26, RR = 0.87, 95% CI = 0.31-0.68) and hospitalizations (LA: 5 versus NON-LA: 4, RR = 1, 95% CI = 0.25-0.74). This cohort strongly suggests that BCG-LA in healthy children is not associated with more episodes of AINF and hospitalizations, when paired and compared with children BCG-vaccinated without BCG-LA.

  9. Non-specific immunity of BCG vaccine: A perspective of BCG immunotherapy

    Directory of Open Access Journals (Sweden)

    Najeeha Talat Iqbal

    2014-01-01

    Full Text Available BCG is a widely used vaccine worldwide for neonates including Pakistan. BCG has more than 90% coverage through the EPI program which was introduced in 1965 in Pakistan. BCG has limited efficacy against the transmissible form of pulmonary tuberculosis in high TB endemic countries. However, BCG vaccination continues in these countries because BCG confers protection against the disseminated form of TB in children. BCG has also shown some protection against leprosy and certain forms of cancers. One reason for such nonspecific protection may be that BCG activates APCs via PAMPS that interacts with TLRs (2, 4 & 8, which initiate the inflammatory cascade thereby recruiting inflammatory cells to the site of infection and providing maturation signals for neutrophils, macrophages and dendritic cells. Such activation may be crucial for restricting the infection at the initial site. Furthermore, activation of the pro-inflammatory cascade also results in expression of adhesion molecules, co-stimulatory molecules as well as MHC class II molecule. MHC class II molecules engage CD4+ cells via the TCR receptor while the adhesion and costimulatory molecules bind to their respective receptors on CD4+ T cells for additional high affinity binding for T cell activation. Although activation of the innate arm may not provide subsequent memory, activation of T cells may introduce a certain level of memory response and therefore, may form a rational basis for BCG immunotherapy. This review, therefore, focuses on the immune activation related to both the innate and adaptive arm of the immune response that has been reported and further explores the utility of BCG immunotherapy related to non TB conditions.

  10. A case of infectious endocarditis due to BCG

    Directory of Open Access Journals (Sweden)

    Alice Fournier

    2015-06-01

    Full Text Available The occurrence of bacillus Calmette–Guérin (BCG disease following instillation for bladder cancer is commonly documented. The intravesical administration of BCG is generally safe, but may present severe complications. A fatal case of native aortic valve infectious endocarditis with septicemia due to BCG in a patient treated with intravesical instillation is reported herein.

  11. BCG protects against tuberculosis irrespective of HIV status

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George

    2013-01-01

    While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

  12. BCG protects toddlers during a tuberculosis outbreak.

    LENUS (Irish Health Repository)

    Gaensbauer, J T

    2009-05-01

    In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

  13. Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

    Science.gov (United States)

    Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beissner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw; Frimpong, Michael; Kabiru, Abass Mohammed; Piten, Ebekalisai; Maman, Issaka; Bidjada, Bawimodom; Koba, Adjaho; Awoussi, Koffi Somenou; Kobara, Basile; Nitschke, Jörg; Wiedemann, Franz Xaver; Kere, Abiba Banla; Adjei, Ohene; Löscher, Thomas; Fleischer, Bernhard; Bretzel, Gisela; Herbinger, Karl-Heinz

    2015-01-01

    Background The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD. PMID:25569674

  14. BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines

    NARCIS (Netherlands)

    Bevers, R. F.; de Boer, E. C.; Kurth, K. H.; Schamhart, D. H.

    1998-01-01

    Intravesical bacillus Calmette-Guerin (BCG) is a successful therapy for superficial bladder cancer. However, the working mechanism of BCG after intravesical instillation is not completely understood. A functional role of urothelial (tumor) cells in the initiation of the BCG-induced immune reaction

  15. [Severe adverse reactions after vaccination with Japanese BCG vaccine: a review].

    Science.gov (United States)

    Toida, Ichiro; Nakata, Shizuko

    2007-11-01

    Japanese BCG vaccine has been admitted by the quality control of World Health Organization (WHO) as the safest BCG vaccine in the world. Even though, BCG, as a live bacterial vaccine, inevitably causes dissemination beyond vaccination site and regional lymph-nodes to various part of the body under certain special conditions. We tried to review the clinical features and immunological status of the cases in which "severe" adverse reactions had developed after vaccination with Japanese freeze-dried BCG vaccine prepared from BCG substrain Tokyo. "Severe" adverse reaction was arbitrarily defined as the adverse reactions of clinical significance developed beyond vaccination site and regional ipsilateral axillary lymph-nodes. By the extensive search of the literatures, 39 cases were identified since 1951 when vaccination with freeze-dried BCG vaccine became compulsory by the Tuberculosis Prevention Law in Japan. Incidence rate was calculated as 0.0182 cases per 100,000 vaccinations. Clinical manifestations of bone and joint were reported in 27 cases (multiple sites: 15 cases, single site: 12 cases), abnormalities in chest X-ray in 13 cases, skin manifestations in 17 cases, diseases in other sites or organs in 8 cases. Most of the cases had lesions in multiple organs. Among these 39 cases, 13 had been diagnosed to have some types of primary immunodeficiency (5 cases: chronic granulomatous disease (CGD); 4 cases: severe combined immunodeficiency (SCID); 4 cases: IFN-gamma receptor 1 deficiency). Further, unidentified defects in cellular immunity were reported in other 6 cases. Death was reported in 6 cases, but in two cases the causes of death were the infections due to different pathogens, namely, pulmonary abscess due to Staphylococcus sp. and bacteremia due to Pseudomonas aeruginosa, respectively, and in only one case death was evidenced as due to disseminated BCG infection by autopsy. All of 6 death cases had some type of immunodeficiency. Apart from fatal cases

  16. Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory

    Science.gov (United States)

    da Costa, Adeliane Castro; Nogueira, Sarah Veloso; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory. PMID:24778634

  17. [The practice of BCG vaccination in 1930 s' China].

    Science.gov (United States)

    Shi, R S

    2017-07-28

    Wang Liang introduced Bacille-Calmatte-Guerin(BCG) to China in 1933 in order to prevent tuberculosis. He established a BCG laboratory and make BCG strains by himself in Chongqing, and vaccinated children around, until he was forced to stop doing it by the government in November, 1937. In 1938 Shanghai Pasteur Institute was established, and they built a BCG laboratory to promote BCG vaccination in Shanghai, and these actions were insisted during 1940s. But in 1930s the medical profession all over the world was skeptical to BCG efficacy, which impeded the promotion of BCG vaccination in China. Without the collaboration of the government and the national medical profession, tuberculosis problem in China couldn't be improved by the effort of single doctor or an institute.

  18. Various ultrasonographic manifestations of Bacille Calmette-Guerin (BCG) lymphadenitis in infants after BCG vaccination

    International Nuclear Information System (INIS)

    Yoon, Choon Sik; Kim, Myung Joon; Lee, Kwang Hun; Kwon, Woo Cheol; Cho, Nariya; Lee, Sung Il; Park, Kae Young; Kim, Dong Jin

    1999-01-01

    To evaluate the various ultrasonographic manifestations of BCG lymphadenitis complicated by BCG vaccination in infants. Among a total of 59 patients of BCG lymphadenitis, we retrospectively evaluated the ultrasonographic findings of five patients (seven involved areas), who were operated and confirmed by histopathology. Three cases were male and two were female and the age range is from 3 months to 9 months (mean: 5.5 months). Among five cases two had only a single lesion and three had multiple lesions, and two of those had multiple lesions at 2 separate locations. All five cases had ipsilateral supraclavicular lesions with same BCG vaccination site and two also had ipsilaeteral axillary lesions. Ultrasonography showed enlarged lymph nodes and heterogeneous hypoechoic changes suggesting internal necrosis or suppurative changes in three cases, but 1 had cystic necrotic change with fluid-fluid level and another had conglomerated mass with intermingled hyper and hypoechoic areas, which were initially suspected to be a tumorous conditions but revealed conglomerated lymph nodes on follow-up ultrasonography and MRI. BCG lymphadenitis is usually located adjacent to a BCG vaccination site, but ultrasonography can show single or multiple lymph node enlargement and various manifestations from homogeneous lymphadenitis to cystic abscess changes and even a mass-like appearance, demonstrating that the evaluation of ultrasonography should be done very carefully.

  19. Age at BCG administration during routine immunization.

    African Journals Online (AJOL)

    Age at BCG administration during routine immunization. R.D. Wammanda , M.J. Gambo and I. Abdulkadir. Department of Paediatrics,. Ahmadu Bello University Teaching Hospital,. Zaria. Correspondence to: Dr.R.D. Wammanda. Email: wammanda@yahoo.com. Summary. In Nigeria, as part of the National Programme on ...

  20. Osteomielitis esternal y escrofuloderma por vacuna BCG.

    Directory of Open Access Journals (Sweden)

    Ivohne Fernanda Corrales

    2003-06-01

    Full Text Available La vacuna BCG se ha usado en todo el mundo desde principios del siglo XX para la prevención de la tuberculosis. Se describe el caso de una niña de 13 meses de edad, previamente sana, que consultó por una masa esternal. El estudio radiológico mostró erosión perióstica. La lesión fue resecada y en la histopatología se encontró una reacción inflamatoria crónica con granulomas caseificantes con compromiso óseo y cutáneo. Se realizó una amplificación por PCR con iniciadores específicos de Mycobacterium tuberculosis del ADN obtenido a partir del tejido incluido en parafina, cuyo resultado fue negativo. Los antecedentes de vacunación con BCG, la aparición de este tipo de granulomas y la ausencia de ADN de M. tuberculosis en el tejido resecado apoyan el diagnóstico de osteomielitis esternal y escrofuloderma por BCG. La osteomielitis es una complicación infrecuente de la vacunación por BCG, que puede presentarse especialmente en pacientes inmunosuprimidos. La evolución clínica de la paciente no ha demostrado ninguna forma de inmunodeficiencia.

  1. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    Directory of Open Access Journals (Sweden)

    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  2. Randomized trial of BCG vaccination at birth to low-birth-weight children

    DEFF Research Database (Denmark)

    Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

    2011-01-01

    Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

  3. Recognition and Treatment of BCG Failure in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Andrew J. Lightfoot

    2011-01-01

    Full Text Available Patients with high-grade Ta, T1, or carcinoma in situ non–muscle-invasive bladder cancer (NMIBC are at high risk for recurrence and, more importantly, progression. Thus, both the American Urological Association and European Association of Urology recommend initial intravesical treatment with bacillus Calmette-Guerin(BCG followed by maintenance therapy for a minimum of 1 year. The complete response rate to BCG therapy in patients with high-risk NMIBC can be as high as ∼80%; however, most patients with high-risk disease suffer from recurrence. BCG failure can be further characterized into BCG refractory, BCG resistant, BCG relapsing, and BCG intolerant. Current recommendations include one further course of BCG or cystectomy. In patients who continue to fail conservative treatment and who refuse surgical therapy or are not surgical candidates, treatment options become even more complicated. In this setting, treatment options are limited and include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy. To date, however, further research is necessary for all secondary treatment options in order to determine which might be the most efficacious. All conservative treatments should be considered investigational. Currently, cystectomy remains the standard of care for high-risk patients who have failed BCG therapy.

  4. IncucyteDRC: An R package for the dose response analysis of live cell imaging data [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Philip J. Chapman

    2016-05-01

    Full Text Available We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web interface, implemented using shiny, is provided for the benefit of non-R users. The software is potentially useful to any research group studying the impact of small molecule inhibitors on cell proliferation using the IncuCyte ZOOM.

  5. Preferences of Informal Carers on Technology Packages to Support Meal Production by People Living with Dementia, Elicited from Personalised AT and ICT Product Brochures

    Directory of Open Access Journals (Sweden)

    Maria Laura De Filippis

    2017-01-01

    Full Text Available Assistive technology (AT can help support the continued independence of people living with dementia, supported by informal carers. Opinions and preferences of informal carers towards a range of assistive and digital information and communication technologies (ICT to support food purchase and menu selection, including navigation and online shopping, and safe meal-making by individuals living with dementia were investigated. General attitudes and experiences with assistive technologies were first probed by means of a focus group with carers (n = 6, organised through the Alzheimer’s Society in Nottingham, England. A series of AT/ICT product brochures were then produced, describing packages of technologies to enable meal production. Task-specific questions were asked of carers (n = 10 at local Memory Cafés as to the perceived capabilities of each individual for shopping and meal-making. Carers were asked to make pair-wise choices in order to select a personalised brochure and to complete a questionnaire to elicit the practicality, desirability and affordability of specific products and to probe for preferences amongst key features. Opinions on ease-of-use, aesthetics, expected safety-in-use, independence of use and stigma related to the technology packages were also collected. Results showed that carers are able to make detailed choices and express preferences about assistive and digital technologies for the individuals in their care, and customise their enabler package. Most believed that having an enabler package would improve safety. Greater exposure of carers to newer digital products would be beneficial. The brochure method could be employed on consumer websites and by AT assessors.

  6. Design and feasibility of a social self-value intervention package to empower people living with HIV.

    Science.gov (United States)

    Bhatta, Dharma Nand; Liabsuetrakul, Tippawan

    2016-09-01

    Human immunodeficiency virus (HIV) infection affects the quality of life of infected people. It is well known that empowerment is important for appropriate access to health care and quality of care. However, there is currently limited availability of explicit methods to increase the empowerment of HIV-infected people. This study aimed to develop and test the feasibility of a social self-value package as an empowerment intervention method for HIV-infected people. One group included 8-10 participants and each session lasted for one and half hours. Six sessions in total were developed and one session was conducted in one week. A total of 66 participants were randomly selected for participating in the package, assessed its feasibility both quantitatively and qualitatively. Attitudes towards HIV-related issues significantly and positively changed after each session. Client satisfaction and acceptability of the intervention was very high indicating high feasibility with good design. The qualitative findings also supported the quantitative findings where both participants and counselors accepted and were satisfied with the structure and contents of the package. This study revealed that providing an inclusive six-week social self-value package for HIV-infected Nepali people appears to be feasible. Its effect on empowerment intervention will be measured by a randomized controlled trial.

  7. Asthmatic Children And Immunological Effects Of BCG Vaccine Key words: Asthmatic children, BCG vaccine

    International Nuclear Information System (INIS)

    Saaed, A.I.

    2011-01-01

    A TH2 screwed immune response is known to play a crucial role in the pathogenesis of allergy, so, preventing the differentiation of TH cells. The TH2 cells are appeared as a logical therapeutic approach to atopic asthma. The purpose of TH1 study was to determine the possible role of BCG vaccine on asthma and whether a TH1 type immune response elicited by BCG immunization could suppress the allergic sensitization in childhood asthma. Seventy asthmatic patients (50 atopic and 20 non-atopic) and fifty healthy individuals were subjected to TH1 study. Tuberculin test was performed for all groups then subjects with positive tuberculin test were excluded. The BCG vaccine was given for all groups with assessment of TH1 and TH2 cytokine response by measuring total IgE, IL-4 (for TH2 response) and INF-γ (for TH1 response). Significant reduction in IgE and IL-4, and elevation in INF-γ were determined in group I (atopic asthma) following BCG vaccination. There was non-significant change observed in IgE and IL-4 levels of group II while significant reduction in IL-4 and significant increase in INF-γ was observed after BCG vaccine

  8. Rodent malaria: BCG-induced protection and immunosuppression

    International Nuclear Information System (INIS)

    Smrkovski, L.L.; Strickland, G.T.

    1978-01-01

    One dose of 10 7 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10 4 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

  9. [BCG vaccination--controversy and compromise].

    Science.gov (United States)

    Petrini, B

    2000-11-29

    In Sweden, BCG-vaccination is recommended to certain risk groups only, as the incidence of TB is very low. Children from high-endemic areas, as well as health care personnel, especially those working in risk areas, are the most important target groups. The efficacy of BCG vaccination has varied in different investigations, but early Nordic studies have shown approximately 80 percent protection. Vaccination prevents disseminated but not localized pulmonary disease. There are no data supporting revaccination. Today some Swedish children are vaccinated without a clear indication, due to caretakers' fear of TB. The risk of new infection is very low in Sweden today, and is for all practical purposes limited to the closest family members of affected individuals. If large numbers of refugees from high-endemic countries arrive in Sweden, the epidemiological situation must be closely monitored.

  10. Waste package performance assessment

    International Nuclear Information System (INIS)

    Lester, D.H.

    1981-01-01

    This paper describes work undertaken to assess the life-expectancy and post-failure nuclide release behavior of high-level and waste packages in a geologic repository. The work involved integrating models of individual phenomena (such as heat transfer, corrosion, package deformation, and nuclide transport) and using existing data to make estimates of post-emplacement behavior of waste packages. A package performance assessment code was developed to predict time to package failure in a flooded repository and subsequent transport of nuclides out of the leaking package. The model has been used to evaluate preliminary package designs. The results indicate, that within the limitation of model assumptions and data base, packages lasting a few hundreds of years could be developed. Very long lived packages may be possible but more comprehensive data are needed to confirm this

  11. Molecular analysis of Mycobacterium isolates from patients with BCG-induced lymphadenitis

    Directory of Open Access Journals (Sweden)

    Farahnoosh Doustdar

    2015-01-01

    Conclusion: As all of the strains isolated from the patients were confirmed as M. bovis BCG strain Pasteur, the other possible factors causing BCG complications, including BCG overdose, faulty intradermal technique, and disturbance of cellular immunity, must be considered.

  12. BCG Vaccination: Is there light at end of the Tunnel?

    OpenAIRE

    PARTHASARATHY, A; HITT, Sharma

    2010-01-01

    The first Human BCG Vaccine was developed in 1921.Since 1960s billions of beneficiaries have received the vaccine in almost all the countries of the world .However its efficacy has been rated from 0 - 80% in several studies world over which include large randomized/controlled/case-control studies. Since 1974 BCG vaccine was included in the Expanded Program on Immunization(EPI) benefitting approx. 2 billion infants. Despite controversy BCG vaccine efficacy has been established in preventing he...

  13. Tuberculin reaction, BCG scar, and lower female mortality

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik

    2006-01-01

    Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar...... in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific....

  14. Short Communication: Age at BCG administration during routine ...

    African Journals Online (AJOL)

    In Nigeria, as part of the National Programme on Immunization (NPI), BCG should be given at birth. A survey of the ages at which mothers bring their children for BCG vaccination showed that only 22% of children receive their BCG within the first 3 days of life and 36.2% within the first 7 days of life. The place of birth and ...

  15. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Dalbagni, G.; Karnes, R.J.; Shariat, S.; Joniau, S.; Palou, J.; Serretta, V.; Larre, S.; Stasi, S. Di; Colombo, R.; Babjuk, M.; Malmstrom, P.U.; Malats, N.; Irani, J.; Baniel, J.; Cai, T.; Cha, E.; Ardelt, P.; Varkarakis, J.; Bartoletti, R.; Spahn, M.; Pisano, F.; Gontero, P.; Sylvester, R.

    2016-01-01

    BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guerin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade

  16. [BCG vaccine against tuberculosis: its protective effect and vaccination policies].

    Science.gov (United States)

    Pereira, Susan M; Dantas, Odimariles Maria Souza; Ximenes, Ricardo; Barreto, Mauricio L

    2007-09-01

    The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case-control studies and meta-analyses presented separately. The protective effect of the first dose of the BCG vaccine against tuberculosis in its miliary and meningeal forms is high. However, the results vary in relation to the pulmonary form of the disease, with some indicating zero effect and others levels of nearly 80%. Research is being carried out to develop new vaccines that could substitute the BCG or be used as a booster. There are evidences that the protective effect of the BCG vaccine does not increase with a second dose. In spite of its limitations and the expectation that a new tuberculosis vaccine will be developed in the future, the BCG vaccine remains an important tool in controlling the harmful effects of tuberculosis, particularly in countries with medium or high incidence levels of the disease.

  17. Variable BCG efficacy in rhesus populations: Pulmonary BCG provides protection where standard intra-dermal vaccination fails.

    Science.gov (United States)

    Verreck, Frank A W; Tchilian, Elma Z; Vervenne, Richard A W; Sombroek, Claudia C; Kondova, Ivanela; Eissen, Okke A; Sommandas, Vinod; van der Werff, Nicole M; Verschoor, Ernst; Braskamp, Gerco; Bakker, Jaco; Langermans, Jan A M; Heidt, Peter J; Ottenhoff, Tom H M; van Kralingen, Klaas W; Thomas, Alan W; Beverley, Peter C L; Kocken, Clemens H M

    2017-05-01

    M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable protective efficacy in different human populations. In non-human primate studies using rhesus macaques, despite efforts to standardise the model, we have also observed variable efficacy of BCG upon subsequent experimental M. tuberculosis challenge. In the present head-to-head study, we establish that the protective efficacy of standard parenteral BCG immunisation varies among different rhesus cohorts. This provides different dynamic ranges for evaluation of investigational vaccines, opportunities for identifying possible correlates of protective immunity and for determining why parenteral BCG immunisation sometimes fails. We also show that pulmonary mucosal BCG vaccination confers reduced local pathology and improves haematological and immunological parameters post-infection in animals that are not responsive to induction of protection by standard intra-dermal BCG. These results have important implications for pulmonary TB vaccination strategies in the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. BCG and BCG/DNAhsp65 vaccinations promote protective effects without deleterious consequences for experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Zorzella-Pezavento, Sofia Fernanda Gonçalves; Guerino, Clara Pires Fujiara; Chiuso-Minicucci, Fernanda; França, Thais Graziela Donegá; Ishikawa, Larissa Lumi Watanabe; Masson, Ana Paula; Silva, Célio Lopes; Sartori, Alexandrina

    2013-01-01

    A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  19. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Sofia Fernanda Gonçalves Zorzella-Pezavento

    2013-01-01

    Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  20. Invitro immune responses in children following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V

    2006-01-01

    Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

  1. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

    Science.gov (United States)

    Dean, Gillian S; Clifford, Derek; Whelan, Adam O; Tchilian, Elma Z; Beverley, Peter C L; Salguero, Francisco J; Xing, Zhou; Vordermeier, Hans M; Villarreal-Ramos, Bernardo

    2015-01-01

    The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

  2. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

    Directory of Open Access Journals (Sweden)

    Gillian S Dean

    Full Text Available The incidence of bovine tuberculosis (bTB in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

  3. Prevalence of BCG scar among BCG-vaccinated children in a ...

    African Journals Online (AJOL)

    Background: The burden of tuberculosis is high in Nigeria as in other developing countries. The administration of BCG vaccine to neonates is essential in the control of tuberculosis. A scar usually develops 6 – 8 weeks later at the site of vaccination, which can be used clinically as a proof of vaccination. Not all vaccinated ...

  4. Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

    Science.gov (United States)

    Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

    2016-01-01

    Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

  5. Mycobacterium bovis endophthalmitis from BCG immunotherapy for bladder cancer

    NARCIS (Netherlands)

    Gerbrandy, S. J. F.; Schreuders, L. C.; de Smet, M. D.

    2008-01-01

    BACKGROUND: We report a patient who developed BCG endophthalmitis after BCG immunotherapy for bladder cancer. Comparison of this case with 2 other reported cases reveals a similar pattern of elderly, debilitated and immunocompromised patients with poor response to systemic antituberculous therapy in

  6. Murine model of BCG lung infection: Dynamics of lymphocyte ...

    Indian Academy of Sciences (India)

    Unknown

    pulmonary BCG infection. Few T cells in tracheal LN of BCG infected mice produce IFNγ, suggesting that maturational changes associated with migration to the lungs or residence in the lungs enhance the capability of some T cells to produce this cytokine. [Saxena R K, Weissman D, Simpson J and Lewis D M 2002 Murine ...

  7. Poly(I:C)-Encapsulating Nanoparticles Enhance Innate Immune Responses to the Tuberculosis Vaccine Bacille Calmette-Guérin (BCG) via Synergistic Activation of Innate Immune Receptors.

    Science.gov (United States)

    Speth, Martin T; Repnik, Urska; Müller, Elisabeth; Spanier, Julia; Kalinke, Ulrich; Corthay, Alexandre; Griffiths, Gareth

    2017-11-06

    The attenuated live vaccine strain bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3), to enhance the immunogenicity of BCG in mouse bone marrow derived macrophages (BMDM) in vitro. Incorporation of poly(I:C) into NPs protected it against degradation by ribonucleases and increased its uptake by mouse BMDM. Whereas soluble poly(I:C) was ineffective, pIC-NPs strongly enhanced the proinflammatory immune response of BCG-infected macrophages in a synergistic fashion, as evident by increased production of cytokines and induction of nitric oxide synthesis. Using macrophages from mice deficient in key signaling molecules involved in the pathogen recognition response, we identified combined activation of MyD88- and TRIF-dependent TLR signaling pathways to be essential for the synergistic effect between BCG and NP. Moreover, synergy was strongly dependent on the order of the two stimuli, with TLR activation by BCG functioning as the priming event for the subsequent pIC-NP stimulus, which acted through an auto-/paracrine type I interferon (IFN) feedback loop. Our results provide a foundation for a promising new approach to enhance BCG-vaccine immunogenicity by costimulation with NPs. They also contribute to a molecular understanding of the observed synergistic interaction between the pIC-NPs and BCG vaccine.

  8. Foreign body granuloma caused by monosodium glutamate after BCG vaccination.

    Science.gov (United States)

    Chiu, Yao-Kun; Huang, Chao-Cheng; Jeng, Jingyueh; Shiea, Jentaie; Chen, Wei-Jen

    2006-08-01

    We describe a 7-month-old male infant with a foreign body granuloma caused by monosodium glutamate (MSG) after a Bacille Calmette-Guérin (BCG) immunization. A ridged, erythematous, indurated plaque developed over a BCG injection site on his left upper arm 1 month after the first BCG immunization. Biopsy showed multiple noncaseating foreign body granulomas without detectable mycobacteria by both Ziehl-Neelsen stain and polymerase chain reaction assay. Birefringent crystals were identified in the foreign body giant cells with polarized light microscopy. The crystals were further determined to be glutamic acid by the method of fast atom bombardment. Hence, MSG, the only composite of BCG vaccine except the bacillus, was believed to be responsible for the granulomatous foreign body reaction. On review of the literature, we could find no previous report of an adverse reaction of BCG immunization attributable to MSG (glutamic acid).

  9. Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults

    Directory of Open Access Journals (Sweden)

    Piotr Szpakowski

    2015-01-01

    Full Text Available Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG, the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18 and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

  10. Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

    NARCIS (Netherlands)

    Buffen, Kathrin; Oosting, Marije; Quintin, Jessica; Ng, Aylwin; Kleinnijenhuis, Johanneke; Magadi Gopalaiah, Vinod Kumar; van de Vosse, Esther; Wijmenga, Cisca; van Crevel, Reinout; Oosterwijk, Egbert; Grotenhuis, Anne J.; Vermeulen, Sita H.; Kiemeney, Lambertus A.; van de Veerdonk, Frank L.; Chamilos, Georgios; Xavier, Ramnik J.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.

    2014-01-01

    The anti-tuberculosis-vaccine Bacillus Calmette-Guerin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated

  11. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer.

    Directory of Open Access Journals (Sweden)

    Kathrin Buffen

    2014-10-01

    Full Text Available The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β-glucans or BCG. Single nucleotide polymorphisms (SNPs in the autophagy genes ATG2B (rs3759601 and ATG5 (rs2245214 influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG.

  12. Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau.

    Science.gov (United States)

    Frankel, H; Byberg, S; Bjerregaard-Andersen, M; Martins, C L; Aaby, P; Benn, C S; Fisker, A B

    2016-08-31

    Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. During 2011-2013, infants in the Bandim Health Project's urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45days in Cox proportional hazards models. Scar prevalence and size were compared using binomial regression and ranksum tests. Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74-2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06-1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain. BCG strain influences scar prevalence and scar size, and may have sex differential effects on morbidity. BCG strains are currently used interchangeably, but BCG scarring has been linked to subsequent survival. Hence, more research into the health effects of different BCG strains is warranted. Small adjustments of BCG production could potentially lower childhood morbidity and mortality at low cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: implications for replication and genome packaging.

    Science.gov (United States)

    Chaturvedi, Sonali; Rao, A L N

    2014-09-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein-protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Sonali; Rao, A.L.N., E-mail: arao@ucr.edu

    2014-09-15

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER.

  15. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    International Nuclear Information System (INIS)

    Chaturvedi, Sonali; Rao, A.L.N.

    2014-01-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER

  16. Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.

    Directory of Open Access Journals (Sweden)

    Hannah Priyadarshini Gideon

    2010-12-01

    Full Text Available M. tuberculosis (MTB species-specific antigenic determinants of the human T cell response are important for immunodiagnosis and vaccination. As hypoxia is a stimulus in chronic tuberculosis infection, we analyzed transcriptional profiles of MTB subject to 168 hours of hypoxia to test the hypothesis that upregulation by hypoxia might result in gene products being recognized as antigens. We identified upregulation of two region of difference (RD 11 (Rv2658C and Rv2659c, and one RD2 (Rv1986 absent from commonly used BCG strains. In MTB infected persons, the IL-2 ELISpot response to Rv1986 peptides was several times greater than the corresponding IFN-γ response to the reference immunodominant ESAT-6 or CFP-10 antigens. The IL-2 response was confined to two epitopic regions containing residues 61-80 and 161-180. The biggest population of IL-2 secreting T cells was single cytokine positive central memory T cells. The IL-2 response to live MTB bacilli lacking Rv1986 was significantly lower than the response to wild type or mutant complemented with Rv1986. In addition, the IL-2 response to Rv1986 was significantly lower in HIV-TB co-infected persons than in HIV uninfected persons, and significantly increased during antiretroviral therapy. These findings demonstrate that Rv1986 is an immunodominant target of memory T cells and is therefore of relevance when considering the partial efficacy of currently used BCG vaccines and provide evidence for a clinical trial comparing BCG strains.

  17. Improved health among people living with HIV/AIDS who received packages of proven preventive health interventions, Amhara, Ethiopia.

    Directory of Open Access Journals (Sweden)

    Ciara E O'Reilly

    Full Text Available In 2009, basic care packages (BCP containing health products were distributed to HIV-infected persons in Ethiopia who were clients of antiretroviral therapy clinics. To measure health impact, we enrolled clients from an intervention hospital and comparison hospital, and then conducted a baseline survey, and 7 bi-weekly home visits. We enrolled 405 intervention group clients and 344 comparison clients. Intervention clients were more likely than comparison clients to have detectable chlorine in stored water (40% vs. 1%, p<0.001, soap (51% vs. 36%, p<0.001, and a BCP water container (65% vs. 0%, p<0.001 at every home visit. Intervention clients were less likely than comparison clients to report illness (44% vs. 67%, p<0.001 or health facility visits for illness (74% vs. 95%, p<0.001, and had lower median illness scores (1.0 vs. 3.0, p<0.05. Participation in the BCP program appeared to improve reported health outcomes.

  18. Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

    Directory of Open Access Journals (Sweden)

    JoĂŤl Pestel

    2008-06-01

    Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

  19. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  20. Deep sequencing analysis of the heterogeneity of seed and commercial lots of the bacillus Calmette-Guérin (BCG) tuberculosis vaccine substrain Tokyo-172

    Science.gov (United States)

    Wada, Takayuki; Maruyama, Fumito; Iwamoto, Tomotada; Maeda, Shinji; Yamamoto, Taro; Nakagawa, Ichiro; Yamamoto, Saburo; Ohara, Naoya

    2015-01-01

    BCG, only vaccine available to prevent tuberculosis, was established in the early 20th century by prolonged passaging of a virulent clinical strain of Mycobacterium bovis. BCG Tokyo-172, originally distributed within Japan in 1924, is one of the currently used reference substrains for the vaccine. Recently, this substrain was reported to contain two spontaneously arising, heterogeneous subpopulations (Types I and II). The proportions of the subpopulations changed over time in both distributed seed lots and commercial lots. To maintain the homogeneity of live vaccines, such variations and subpopulational mutations in lots should be restrained and monitored. We incorporated deep sequencing techniques to validate such heterogeneity in lots of the BCG Tokyo-172 substrain without cloning. By bioinformatics analysis, we not only detected the two subpopulations but also detected two intrinsic variations within these populations. The intrinsic variants could be isolated from respective lots as colonies cultured on plate media, suggesting analyses incorporating deep sequencing techniques are powerful, valid tools to detect mutations in live bacterial vaccine lots. Our data showed that spontaneous mutations in BCG vaccines could be easily monitored by deep sequencing without direct isolation of variants, revealing the complex heterogeneity of BCG Tokyo-172 and its daughter lots currently in use. PMID:26635118

  1. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+)CD56(bright) cells.

    Science.gov (United States)

    Portevin, Damien; Young, Douglas

    2013-01-01

    Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK) cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright) NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright) population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright) NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright) cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  2. STUDY OF BCG SCAR AND SERUM ADA LEVELS IN INFANTS

    Directory of Open Access Journals (Sweden)

    Harishchandra Venkata Yanamandala

    2017-11-01

    Full Text Available BACKGROUND In developing countries, in both adults and children, tuberculosis is an important cause of morbidity and mortality. In 1993, it is declared as the first infectious disease by global health emergency.1 According to WHO report globally, there were an estimated 9.27 million ancient cases of TB in 2009. The cases reported were 8.3 million, the children covered an estimated percentage of 11 and it ranged from 3-25 percent.2 BCG vaccination was advocated for prevention of tuberculosis in children. The aim of the study is to estimate serum ADA levels in newborns before BCG vaccination, serum ADA levels in children with and without BCG scar, after receiving BCG vaccination, serum ADA levels in children without BCG vaccination and to find significance of serum ADA levels in BCG vaccinated children by comparing the above groups. MATERIALS AND METHODS This study was conducted at the Department of Paediatrics, Gitam Institute of Medical Sciences and Research Institute, October 2015 to September 2016. Babies who were in postnatal ward and infants of age of 12 weeks attending for BCG vaccination were included in the study. The total numbers of infants studied were 150. RESULTS In our study, out of 120 children included in the study before BCG vaccination comprising group-1, 61% were males and 39% were females. Out of 120 children received BCG vaccination, only 100 came for follow up comprising group-2, of which 67 (67% were males and 33 (33% were females. 15 children who did not receive BCG vaccination at 12 weeks of age were included in group 3 out of which 11 (73.33% were males and 4 (26.67% were females. Mean ADA levels at the age of 12 weeks in group-2 who were vaccinated at birth were 30.89 ± 5.27 U/L compared to mean ADA levels at the age of 12 weeks in group-3, which was 15.47 ± 1.85 U/L. This shows significant rise in mean ADA levels at 12 weeks of age in those who were vaccinated at birth comprising group-2 compared to their mean ADA

  3. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  4. Hubungan antara Pembentukan Scar Vaksin BCG dan Kejadian Infeksi Tuberkulosis

    Directory of Open Access Journals (Sweden)

    Fajriah Rosandali

    2016-08-01

    Full Text Available AbstrakTuberkulosis adalah penyakit menular yang disebabkan oleh kuman Mycobacterium tuberculosis. Orang dewasa yang menderita tuberkulosis sangat mudah menularkan kuman TB kepada orang disekitarnya terutama pada anak-anak. Salah satu cara pencegahan penyakit tuberkulosis adalah pemberian imunisasi BCG pada saat bayi baru lahir. Scar vaksin BCG dapat terbentuk setelah penyuntikan, kadang Scar tidak terbentuk setelah penyuntikan. Tujuan penelitian ini adalah menentukan hubungan antara pembentukan Scar vaksin BCG dan kejadian infeksi tuberkulosis. Penelitian ini menggunakan desain cross sectional dengan jumlah subjek sebanyak 80 orang. Pengambilan data berupa melakukan pengamatan terhadap Scar pada lengan atas serta wawancara kepada responden dengan menggunakan pedoman wawancara. Kemudian data ditabulasi dalam bentuk persentase dan dianalisis dengan uji chi-square . Hasil penelitian menunjukan bahwa responden yang terbanyak adalah perempuan dan usia yang terbanyak 35-44 tahun. Terdapat hubungan yang bermakna antara pembentukan Scar  vaksin BCG dengan kejadian infeksi tuberkulosis (p < 0,05. Disimpulkan bahwa terdapat pengaruh antara pembentukan Scar vaksin BCG terhadap kejadian infeksi tuberkulosis.Kata kunci: tuberkulosis, vaksin BCG, Scar. AbstractTuberculosis is an infectious disease caused by Mycobacterium tuberculosis with the number of sufferers tend to increase every years. Adults who suffer  tuberculosis is very easy to spread it to around, especially to children. One of the way to prevent tuberculosis is immunization of BCG vaccine which given since infant. The Scar of BCG vaccine can formed after injection or not. The objective of this study was to determine the relation of BCG vaccine Scar formation on  the incidence of tuberculosis infection.This research used a cross sectional design with 80 total subjects. The data was collected by observations of the scar on the upper arm while interviewed  respondents using interview guide

  5. Reaction of the BCG Scar in the Acute Phase of Kawasaki Disease in Mexican Children.

    Science.gov (United States)

    Garrido-García, Luis Martín; Castillo-Moguel, Ariel; Vázquez-Rivera, Mirella; Cravioto, Patricia; Fernando, Galván

    2017-10-01

    Kawasaki disease (KD) is an acute self-limited systemic vasculitis that primarily affects children BCG) inoculation site has been reported as a common finding in patients with KD where BCG vaccination is mandatory. The purpose of this study was to evaluate the frequency of reactivation of the BCG in Mexican children diagnosed with KD. A retrospective study of all patients diagnosed with KD from August 1, 1995, to August 31, 2015, at our Institution was performed. The clinical profile, laboratory results, treatment used and coronary artery abnormalities in the BCG reactive and the BCG nonreactive groups were analyzed and compared. We included 399 patients with KD. Ninety-seven (24.3%) had BCG reaction at the inoculation site. The BCG(+) group was younger than the BCG(-) group (P BCG(+) group compared with 65 (21.52%) in the BCG(-) group without statistical significance. The BCG+ group developed coronary artery aneurysms in 37 cases and the BCG(-) group developed coronary artery aneurysms in 111 cases without statistical significance. Multivariate analysis showed that younger age at diagnosis was the only variable associated with a reaction at the BCG inoculation site in patients with KD. In Mexico, a country with a National BCG Vaccination Program and a low incidence of KD, reaction at the BCG inoculation site could be a useful diagnostic sign of KD.

  6. Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

    DEFF Research Database (Denmark)

    Frankel, H; Byberg, S; Andersen, Morten Bjerregaard

    2016-01-01

    BACKGROUND: Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. METHODS: During 2011-2013, infants in the Bandim Health Project......'s urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45days in Cox proportional hazards...... models. Scar prevalence and size were compared using binomial regression and ranksum tests. RESULTS: Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG...

  7. Attrition of T-Cell Functions and Simultaneous Upregulation of Inhibitory Markers Correspond with the Waning of BCG-Induced Protection against Tuberculosis in Mice

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Posey, James E.; Amara, Rama Rao; Sable, Suraj B.

    2014-01-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4+ and CD8+ T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4+ and CD8+ T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4+ T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4+ and CD8+ T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis. PMID:25419982

  8. BCG vaccination at birth and early childhood hospitalization

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter

    2017-01-01

    BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG...... vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age.......94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. CONCLUSIONS: BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15...

  9. THE ABELL 85 BCG: A NUCLEATED, CORELESS GALAXY

    Energy Technology Data Exchange (ETDEWEB)

    Madrid, Juan P. [Gemini Observatory, Southern Operations Center, Colina El Pino s/n, La Serena (Chile); Donzelli, Carlos J. [Instituto de Astronomía Teórica y Experimental, CONICET-UNC, Laprida 922, Córdoba (Argentina)

    2016-03-01

    New high-resolution r-band imaging of the brightest cluster galaxy (BCG) in Abell 85 (Holm 15A) was obtained using the Gemini Multi Object Spectrograph. These data were taken with the aim of deriving an accurate surface brightness profile of the BCG of Abell 85, in particular, its central region. The new Gemini data show clear evidence of a previously unreported nuclear emission that is evident as a distinct light excess in the central kiloparsec of the surface brightness profile. We find that the light profile is never flat nor does it present a downward trend toward the center of the galaxy. That is, the new Gemini data show a different physical reality from the featureless, “evacuated core” recently claimed for the Abell 85 BCG. After trying different models, we find that the surface brightness profile of the BCG of Abell 85 is best fit by a double Sérsic model.

  10. Disseminated BCG infection in a patient with severe combined immunodeficiency

    International Nuclear Information System (INIS)

    Han, Tae Il; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

    2000-01-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy

  11. Disseminated BCG infection in a patient with severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2000-06-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  12. Packaging fluency

    DEFF Research Database (Denmark)

    Mocanu, Ana; Chrysochou, Polymeros; Bogomolova, Svetlana

    2011-01-01

    Research on packaging stresses the need for packaging design to read easily, presuming fast and accurate processing of product-related information. In this paper we define this property of packaging as “packaging fluency”. Based on the existing marketing and cognitive psychology literature...... on packaging design and processing fluency, our aim is to define and conceptualise packaging fluency. We stress the important role of packaging fluency since it is anticipated that a fluent package would influence the evaluative judgments for a product. We conclude this paper by setting the research agenda...

  13. Cytochemical and biological properties of Mycobacterium bovis BCG.

    Science.gov (United States)

    Slosárek, M

    1977-01-01

    It was the aim of the present communication to find a simple test for a reliable discrimination of Mycobacterium bovis BCG from Mycobacterium tuberculosis. A total of 26 BCG strains, out of them 10 Czechoslovak strains (2 lyophilized cultures of BCG of different batch, 6 strains isolated from abscesses of children after BCG-vaccination and 2 strains from fatal cases after BCG-vaccination) and 16 strains obtained from foreign laboratories, were used. Of the tested characteristics a combination of 3 tests, sensitivity to 1 microgram of 2-thiophene carbonylhydrazide (TCH), activity of 3 acylamidases (urease, nicotinamidase and pyrazinamidase) and a quantitative nitrate test, was found to be most advantageous. The Czechoslovak strains of Mycobacterium bovis BCG were fully sensitive to TCH, of the 3 acylamidases mentioned above only urease was positive and nitrate was reduced only little or not at all. On the other hand, strains of Mycobacterium tuberculosis were always resistant to TCH, had positive urease, nicotinamidase and pyrazinamidase and reduced nitrate very intensively.

  14. BCG and protection against inflammatory and auto-immune diseases.

    Science.gov (United States)

    Kowalewicz-Kulbat, Magdalena; Locht, Camille

    2017-07-01

    Bacillus Calmette-Guérin (BCG) is the only available vaccine against tuberculosis. Although its protective efficacy against pulmonary tuberculosis is still under debate, it provides protection against other mycobacterial diseases. BCG is also an effective therapy against superficial bladder cancer and potentially decreases overall childhood mortality. Areas covered: The purpose of this paper is to provide a state-of-the-art summary of the beneficial effects of BCG in inflammatory and auto-immune diseases. As a strong inducer of Th1 type immunity, BCG has been reported to protect against atopic conditions, such as allergic asthma, a Th2-driven disorder. Its protective effect has been well documented in mice, but still awaits definitive evidence in humans. Similarly, murine studies have shown a protective effect of BCG against auto-immune diseases, such as multiple sclerosis and insulin-dependent diabetes, but studies in humans have come to conflicting conclusions. Expert commentary: Studies in mice have shown a beneficial effect of the BCG vaccine against allergic asthma, multiple sclerosis and diabetes. However, the understanding of its mechanism is still fragmentary and requires further in depth research. Some observational or intervention studies in humans have also suggested a beneficial effect, but definitive evidence for this requires confirmation in carefully conducted prospective studies.

  15. Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

    Science.gov (United States)

    Pereira, V B; da Cunha, V P; Preisser, T M; Souza, B M; Turk, M Z; De Castro, C P; Azevedo, M S P; Miyoshi, A

    2017-06-01

    A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system. © 2017 The Society for Applied Microbiology.

  16. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2013-01-01

    Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

  17. Persistence of the immune response induced by BCG vaccination

    Directory of Open Access Journals (Sweden)

    Blitz Rose

    2008-01-01

    Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

  18. Microelectronic packaging

    CERN Document Server

    Datta, M; Schultze, J Walter

    2004-01-01

    Microelectronic Packaging analyzes the massive impact of electrochemical technologies on various levels of microelectronic packaging. Traditionally, interconnections within a chip were considered outside the realm of packaging technologies, but this book emphasizes the importance of chip wiring as a key aspect of microelectronic packaging, and focuses on electrochemical processing as an enabler of advanced chip metallization.Divided into five parts, the book begins by outlining the basics of electrochemical processing, defining the microelectronic packaging hierarchy, and emphasizing the impac

  19. BCG vaccination in southern rural Mozambique: an overview of coverage and its determinants based on data from the demographic and health surveillance system in the district of Manhiça.

    Science.gov (United States)

    Marbán-Castro, Elena; Sacoor, Charfudin; Nhacolo, Ariel; Augusto, Orvalho; Jamisse, Edgar; López-Varela, Elisa; Casellas, Aina; Aponte, John J; Bassat, Quique; Sigauque, Betuel; Macete, Eusebio; Garcia-Basteiro, Alberto L

    2018-02-13

    Over the past four decades, the World Health Organization established the Expanded Programme on Immunization (EPI) to foster universal access to all relevant vaccines for all children at risk. The success of this program has been undeniable, but requires periodic monitoring to ensure that coverage rates remain high. The aim of this study was to measure the BCG vaccination coverage in Manhiça district, a high TB burden rural area of Southern Mozambique and to investigate factors that may be associated with BCG vaccination. We used data from the Health and Demographic Surveillance System (HDSS) run by the Manhiça Health Research Centre (CISM) in the district of Manhiça. A questionnaire was added in the annual HDSS round visits to retrospectively collect the vaccination history of children under the age of 3 years. Vaccinations are registered in the National Health Cards which are universally distributed at birth. This information was collected for children born from 2011 to 2014. Data on whether a child was vaccinated for BCG were collected from these National Health Cards and/or BCG scar assessment. A total of 10,875 number of children were eligible for the study and 7903 presented the health card. BCG coverage was 97.4% for children holding a health card. A BCG-compatible scar was observed in 99.0% of all children and in 99.6% of children with recorded BCG in the card. A total of 93.4% of children had been vaccinated with BCG within their first 28 days of life. None of the factors analysed were found to be associated with lack of BCG vaccination except for living in the municipality of Maluana compared to living in the municipality of Manhiça; (OR = 1.89, 95% CI: 1.18-3.00). Coverage for other EPI vaccines during the first year of life was similarly high, but decreased for subsequent doses. BCG coverage is high and timely administered. Almost all vaccinated infants develop scar, which is a useful proxy for monitoring BCG vaccine implementation.

  20. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Witjes, J Alfred; Dalbagni, Guido; Karnes, Robert J; Shariat, Shahrokh; Joniau, Steven; Palou, Joan; Serretta, Vincenzo; Larré, Stéphane; di Stasi, Savino; Colombo, Renzo; Babjuk, Marek; Malmström, Per-Uno; Malats, Nuria; Irani, Jacques; Baniel, Jack; Cai, Tommaso; Cha, Eugene; Ardelt, Peter; Varkarakis, John; Bartoletti, Riccardo; Spahn, Martin; Pisano, Francesca; Gontero, Paolo; Sylvester, Richard

    2016-11-01

    Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; PBCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. BCG and Adverse Events in the Context of Leprosy

    Directory of Open Access Journals (Sweden)

    Renate Richardus

    2018-04-01

    Full Text Available BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (revaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae antigens in overnight whole-blood assays (WBA. M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34% presented with adverse events, mainly (80% consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60% had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1 in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective

  2. Ultraviolet susceptibility of BCG and virulent tubercle bacilli

    International Nuclear Information System (INIS)

    Riley, R.L.; Knight, M.; Middlebrook, G.

    1976-01-01

    To test the effectiveness of irradiating the upper air of a room with ultraviolet light at reducing the concentration of airborne tubercle bacilli, the susceptibility to the germicidal effects of ultraviolet light, Z, was determined for various mycobacteria. Virulent tubercle bacilli and bacille Calmette-Guerin (BCG) were susceptible to ultraviolet radiation, whereas Mycobacterium phlei had 10 times their resistance (Z, approximately one-tenth that for M. tuberculosis). The effectiveness against BCG of upper air ultraviolet irradiation in a room was tested directly by nebulizing BCG into the air of the room and monitoring its rate of disappearance. With one 17-watt fixture operating, the rate of disappearance increased 6-fold; with 2 fixtures operating (46 watts total), the rate of disappearance increased 9-fold. This implies that under steady-state conditions, the concentrations of airborne organisms with ultraviolet light(s) on would have been one-sixth and one-ninth, respectively. The increase in rate of decay of the airborne organism using 1 fixture was equivalent to 10 air changes per hour, whereas that using 2 fixtures was approximately 25 air changes per hour (range: 18 to 33 air changes per hour). These increments are less than those reported previously for Serratia marcescens, because the Z value for BCG is approximately one-seventh that for serratia. These findings with BCG are believed to be directly applicable to virulent tubercle bacilli

  3. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  4. Think INSIDE the Box: Package Engineering

    Science.gov (United States)

    Snyder, Mark; Painter, Donna

    2014-01-01

    Most products people purchase, keep in their homes, and often discard, are typically packaged in some way. Packaging is so prevalent in daily lives that many of take it for granted. That is by design-the expectation of good packaging is that it exists for the sake of the product. The primary purposes of any package (to contain, inform, display,…

  5. Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis.

    Science.gov (United States)

    Sander, Peter; Clark, Simon; Petrera, Agnese; Vilaplana, Cristina; Meuli, Michael; Selchow, Petra; Zelmer, Andrea; Mohanan, Deepa; Andreu, Nuria; Rayner, Emma; Dal Molin, Michael; Bancroft, Gregory J; Johansen, Pål; Cardona, Pere-Joan; Williams, Ann; Böttger, Erik C

    2015-03-10

    Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG Δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG Δzmp1 for use in clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

    Directory of Open Access Journals (Sweden)

    Stephen P Carter

    Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

  7. Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease.

    Science.gov (United States)

    Steinberg, Ryan L; Thomas, Lewis J; Mott, Sarah L; O'Donnell, Michael A

    2016-04-27

    Objective: To create the first data-driven definition for those unlikely to benefit from further BCG treatment. Materials and Methods: The database created for the Phase 2 BCG-Interferon- α 2B (IFN) study was queried and BCG failure patients were identified ( n  = 334). Full study protocols have previously been published. Separate models were constructed for analysis of patients with any CIS (pure or concomitant) and pure papillary disease. Variables considered included age, gender, stage, grade, tumor size and focality (for papillary only), number of prior BCG courses, and prior BCG failure interval. Results: Patients with recurrent CIS within 6 months of their most recent prior BCG course (HR 2.56, p  disease within 6 months (HR 1.82, p  = 0.02), ≥2 BCG failures (HR 1.54, p  = 0.03), and multifocal disease (HR 2.05, p  disease remained disease free in 38% of cases (24-51% 95% CI) at 2 years with low rates of progression. Conclusions: Patients who fail two courses of BCG with either persistent or recurrent multifocal papillary disease within 6 months or CIS within 12 months of their prior BCG should be considered BCG unresponsive. Recurrent T1 disease respond reasonably well to another course with low progression rates but further investigation is warranted.

  8. Post-Vaccination disseminated BCG infection in an 8-month-old infant

    Directory of Open Access Journals (Sweden)

    fariba Tarhani

    2004-06-01

    Conclusions: Although the BCG vaccine has been in use since 1921 and its protective effect for disseminated, meningial and pulmonary tuberculosis is clear, controversy continues around its use. The most serious complication of BCG vaccine is a disseminated BCG infection that may lead to death.

  9. BCG vaccination scar associated with better childhood survival in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Gustafson, Per; Nhaga, Alexandro

    2005-01-01

    Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death....

  10. Inhibition of natural killer cell-mediated cytotoxicity by lipids extracted from Mycobacterium bovis BCG

    NARCIS (Netherlands)

    Roozemond, R. C.; Halperin, M.; Das, P. K.

    1985-01-01

    Several studies have demonstrated an augmentation of natural killer (NK) cell-mediated cytotoxicity by various adjuvants including BCG. Inhibitory effects of BCG have also been reported, particularly for relatively high doses. Because the cell wall of Mycobacterium bovis BCG contains a high

  11. Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost?

    Science.gov (United States)

    Khademi, Farzad; Derakhshan, Mohammad; Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen; Soleimanpour, Saman

    2018-01-01

    More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG. Expert commentary: Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.

  12. Interruption of persistent exposure to leprosy combined or not with recent BCG vaccination enhances the response to Mycobacterium leprae specific antigens.

    Science.gov (United States)

    de Carvalho, Fernanda Marques; Rodrigues, Luciana Silva; Duppre, Nádia Cristina; Alvim, Iris Maria Peixoto; Ribeiro-Alves, Marcelo; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pessolani, Maria Cristina Vidal; Pereira, Geraldo Moura Batista

    2017-05-01

    Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-β, IL-6, IL-17, TNF, IFN-γ, MIP1-β, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through "trained immunity", that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.

  13. Immunotherapy with BCG cell wall plus irradiated tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizukuro, Tomoyuki (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-04-01

    Two different fibrosarcomas (MCB-I, MCB-II) were induced by methylcholcholanthrene in syngeneic Balb/C mice were used. The tumor cells irradiated with 5,000 to 30,000 rads did not growth in mice on 30 days after inoculation. The viable tumor cells were challenged intradermally to mice on 7 days after inoculation of the tumor cells irradiated with 5,000 to 30,000 rads. The challenged tumor cells were all rejected at 30 days after inoculation. Mice were challenged with 5 x 10/sup 5/ viable tumor cells on 7 days after inoculation of 10/sup 3/ to 10/sup 8/ irradiated tumor cells. Mice pretreated with 10/sup 5/ or 10/sup 6/ irradiated tumor cells rejected the tumor cells completely. The viable tumor cells were challenged to mice on 7 days after inoculation of BCG-CW emulsion plus 10/sup 6/ irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 10/sup 6/ irradiated tumor cells. Optimal dosage of BCG-CW emulsion was 50 or 100 mu g. BCG-CW emulsion plus irradiated tumor cells were injected subcutaneously to the mice after tumor cells inoculation. Three injections of the vaccine significantly suppressed the tumor outgrowth, but not one or two injections in no-treated mice. However, in the mice pretreated with BCG-CW emulsion, the tumor growth was significantly suppressed by one or two injections of the vaccine. Especially, the three injections of the vaccine significantly suppressed the tumor growth and the 25% of the mice were completely cured. The effect of the vaccine was almost the same grade by contralateral or ipsilateral treatment. The irradiated MCB-II tumor cells plus BCG-CW emulsion were not effective to the MCB-1 tumor bearing mice, suggesting the anti-tumor effect of this vaccine was immunologically specific.

  14. MEMS packaging

    CERN Document Server

    Hsu , Tai-Ran

    2004-01-01

    MEMS Packaging discusses the prevalent practices and enabling techniques in assembly, packaging and testing of microelectromechanical systems (MEMS). The entire spectrum of assembly, packaging and testing of MEMS and microsystems, from essential enabling technologies to applications in key industries of life sciences, telecommunications and aerospace engineering is covered. Other topics included are bonding and sealing of microcomponents, process flow of MEMS and microsystems packaging, automated microassembly, and testing and design for testing.The Institution of Engineering and Technology is

  15. Cutaneous necrotic ulceration due to BCG re-vaccination

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Andersen, Ase Bengård; Halkjær, Liselotte Brydensholt

    2012-01-01

    The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature.......The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature....

  16. Color in packaging design : Case: ZheJiang JinSheng packaging Co,Ltd

    OpenAIRE

    Hu, Cuicui

    2010-01-01

    Color occupies an important position in packaging design, with the improvement of living standard, the higher requirement of color design in packaging. The aim of this thesis was to discuss key issues concerning aesthetics of packaging design. Topics will include an overview of the packaging design, the influence factor of packaging design, and introduce the aesthetics from packaging aspect. This thesis will also identify common problems of the production process, and list the phases of ho...

  17. Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection.

    Science.gov (United States)

    Orduña, Patricia; Cevallos, Miguel A; de León, Samuel Ponce; Arvizu, Adriana; Hernández-González, Ismael L; Mendoza-Hernández, Guillermo; López-Vidal, Yolanda

    2011-10-08

    Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests. BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.

  18. Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

    Directory of Open Access Journals (Sweden)

    López-Vidal Yolanda

    2011-10-01

    Full Text Available Abstract Background Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. Results BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1, RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01, 655 (RDMex02 and 2,847 bp (REDMex03 long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests. Conclusions BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03. The loss of RDMex02 (fadD23 is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.

  19. Ipr1 modified BCG as a novel vaccine induces stronger immunity than BCG against tuberculosis infection in mice.

    Science.gov (United States)

    Wang, Yuwei; Yang, Chun; He, Yonglin; Zhan, Xingxing; Xu, Lei

    2016-08-01

    Tuberculosis is a major challenge to global public health. However, the Bacille Calmette‑Guérin (BCG), the only vaccine available against tuberculosis, has been questioned for the low protective effect. The present study used the mouse gene intracellular pathogen resistance I (Ipr1) gene to alter the current BCG vaccine and evaluated its immunity effect against tuberculosis. This study also investigated the intrinsic relationships of Ipr1 and innate immunity. The reformed BCG (BCGi) carrying the Ipr1 gene was constructed. The mice were intranasally challenged with the M. tuberculosis H37Rv strain after vaccination with BCGi. Protection efficacy of the vaccine was assessed by the organ coefficient, bacterial load and pathological changes in the lung. The differential expression of 113 immune‑related genes between BCGi and BCG groups were detected by an oligo microarray. According to the results of organ coefficient, bacterial load and pathological changes in the organization, BCGi had been shown to have stronger protective effects against M. tuberculosis than BCG. The oligo microarray and reverse transcription‑quantitative polymerase chain reaction further revealed that the Ipr1 gene could upregulate the expression of 13 genes, including a >3‑fold increase in Toll‑like receptor (TLR)4 and 10‑fold increase in surfactant protein D (sftpd). The two genes not only participate in innate immunity against pathogens, but also are closely interrelated. Ipr1 could activate the TLR4 and sftpd signaling pathway and improve the innate immunity against tuberculosis, therefore Ipr1 modified BCG may be a candidate vaccine against M. tuberculosis.

  20. Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer

    Science.gov (United States)

    Pérez-Jacoiste Asín, María Asunción; Fernández-Ruiz, Mario; López-Medrano, Francisco; Lumbreras, Carlos; Tejido, Ángel; San Juan, Rafael; Arrebola-Pajares, Ana; Lizasoain, Manuel; Prieto, Santiago; Aguado, José María

    2014-01-01

    Abstract Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0–9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with

  1. An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

    Science.gov (United States)

    Romano, Marta; Huygen, Kris

    2012-12-01

    Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

  2. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

    2017-01-01

    Introduction BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG......) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. Methods Within 7 days after birth, children were randomised 1:1 to BCG vaccination...... included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by ‘age at randomisation’ we found a possible inducing effect of BCG on antibodies against B...

  3. BCG vaccination status of children with tuberculous meningitis and ...

    African Journals Online (AJOL)

    From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with ...

  4. BCG vaccination status of children with tuberculous meningitis and ...

    African Journals Online (AJOL)

    From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child. Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with.

  5. Immunometabolic Pathways in BCG-Induced Trained Immunity

    NARCIS (Netherlands)

    Arts, R.J.; Carvalho, A.; Rocca, C. La; Palma, C.; Rodrigues, F.; Silvestre, R.; Kleinnijenhuis, J.; Lachmandas, E.; Goncalves, L.G.; Belinha, A.; Cunha, C.; Oosting, M.; Joosten, L.A.; Matarese, G.; Crevel, R. van; Netea, M.G.

    2016-01-01

    The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity.

  6. Surgical management of BCG vaccine-induced regional axillary ...

    African Journals Online (AJOL)

    The age of the patient and mode of presentation, imaging findings, and results of tuberculin skin testing (Mantoux test) ... Primary surgical treatment (incisional drainage or biopsy) is therefore not considered an ideal form of management in BCG lymphadenitis because of the high fistulisation and poor wound healing, ...

  7. Original Article Failure of Bacillus Calmette Guerin (BCG) Therapy ...

    African Journals Online (AJOL)

    Administrator

    a second tumor recurrence or progression according to the tumor aggressiveness and the patient's preference. Keywords : Superficial bladder cancer, Bacillus Calmette Guerin (BCG), tumor .... from the remaining bladder in high-risk pa- tients. Statistical analysis was performed with. Student's t-test and Chi-square test and.

  8. Immunometabolic Pathways in BCG-Induced Trained Immunity.

    Science.gov (United States)

    Arts, Rob J W; Carvalho, Agostinho; La Rocca, Claudia; Palma, Carla; Rodrigues, Fernando; Silvestre, Ricardo; Kleinnijenhuis, Johanneke; Lachmandas, Ekta; Gonçalves, Luís G; Belinha, Ana; Cunha, Cristina; Oosting, Marije; Joosten, Leo A B; Matarese, Giuseppe; van Crevel, Reinout; Netea, Mihai G

    2016-12-06

    The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Diffuse bony involvement in disseminated BCG disease in a patient ...

    African Journals Online (AJOL)

    BCG (bacille Calmette-Guérin) vaccination is carried out worldwide to prevent tuberculosis. It is considered to be very effective and has an excellent safety profile, but complications do occur. These may range from erythema and abscess at the site of inoculation to extensive disseminated disease including regional and ...

  10. BCG vaccination at birth and early childhood hospitalisation

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter

    2017-01-01

    vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age....... Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per...... compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0...

  11. The Swarm Magnetometry Package

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Jørgensen, John Leif; Friis-Christensen, Eigil

    2008-01-01

    The Swarm mission under the ESA's Living Planet Programme is planned for launch in 2010 and consists of a constellation of three satellites at LEO. The prime objective of Swarm is to measure the geomagnetic field with unprecedented accuracy in space and time. The magnetometry package consists...

  12. [CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

    Science.gov (United States)

    Tsukaguchi, K; Okamura, H; Tokuyama, T; Okamoto, Y; Fu, A; Yamamoto, C; Nakaya, M; Kobayashi, A; Yoneda, T; Narita, N

    1997-12-01

    We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

  13. Packaging microservices

    DEFF Research Database (Denmark)

    Montesi, Fabrizio; Thrane, Dan Sebastian

    2017-01-01

    We describe a first proposal for a new packaging system for microservices based on the Jolie programming language, called the Jolie Package Manager (JPM). Its main features revolve around service interfaces, which make the functionalities that a service provides and depends on explicit. For the f......We describe a first proposal for a new packaging system for microservices based on the Jolie programming language, called the Jolie Package Manager (JPM). Its main features revolve around service interfaces, which make the functionalities that a service provides and depends on explicit...

  14. Determinants of BCG scarification among children in rural Guinea-Bissau: A prospective cohort study.

    Science.gov (United States)

    Funch, Katarina M; Thysen, Sanne M; Rodrigues, Amabelia; Martins, Cesario L; Aaby, Peter; Benn, Christine S; Fisker, Ane B

    2018-01-02

    Bacillus Calmette-Guérin (BCG) vaccination may have beneficial non-specific effects on child survival, the effects being stronger for children developing a scar. In a prospective cohort study, we examined determinants for not developing a BCG scar within 6 months of vaccination. Bandim Health Project (BHP) runs a Health and Demographic Surveillance System site in rural Guinea-Bissau. BHP provides BCG at monthly visits. We studied determinants for not developing a BCG scar using binomial regression models to obtain relative risks (RR). From May 2012 until October 2014, BHP nurses vaccinated 2415 infants with BCG. We assessed BCG scar between 6 and 12 months of age for 2156 (89%) of these children and 2115 (98%) had developed a scar. In comparison, among 785 children BCG vaccinated elsewhere, 622 (79%) had a scar, the RR of not having a scar being 10.91 (7.52-15.85) compared with children vaccinated by BHP. Among children vaccinated by BHP, those receiving the Russian BCG strain were more likely not to develop a scar (RR = 2.98 (1.52-5.81)) compared with children receiving Danish BCG strain. Children with no post-injection wheal or a wheal BCG scar development while nutritional status and socioeconomic status were not. Scarring rate may therefore be a better indicator of vaccination programme performance than coverage.

  15. Loss of Lipid Virulence Factors Reduces the Efficacy of the BCG Vaccine

    Science.gov (United States)

    Tran, Vanessa; Ahn, Sang Kyun; Ng, Mark; Li, Ming; Liu, Jun

    2016-01-01

    Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. BCG comprises a number of substrains that exhibit genetic and biochemical differences. Whether and how these differences affect BCG efficacy remain unknown. Compared to other BCG strains, BCG-Japan, -Moreau, and -Glaxo are defective in the production of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), two lipid virulence factors. To determine if the loss of PDIMs/PGLs affects BCG efficacy, we constructed a PDIM/PGL-deficient strain of BCG-Pasteur by deleting fadD28, and compared virulence, immunogenicity, and protective efficacy in animal models. SCID mouse infection experiments showed that ∆fadD28 was more attenuated than wild type (WT). The ∆fadD28 and WT strains induced equivalent levels of antigen specific IFN-γ by CD4+ and CD8+ T cells; however, ∆fadD28 was less effective against Mycobacterium tuberculosis challenge in both BALB/c mice and guinea pigs. These results indicate that the loss of PIDMs/PGLs reduces the virulence and protective efficacy of BCG. Since the loss of PDIMs/PGLs occurs naturally in a subset of BCG strains, it also suggests that these strains may have been over-attenuated, which compromises their effectiveness. Our finding has important implications for current BCG programs and future vaccine development. PMID:27357109

  16. The Moreau Strain of Bacillus Calmette-Guerin (BCG) for High-Risk Non-Muscle Invasive Bladder Cancer: An Alternative during Worldwide BCG Shortage?

    Science.gov (United States)

    Hofbauer, Sebastian L; Shariat, Shahrokh F; Chade, Daher C; Sarkis, Alvaro S; Ribeiro-Filho, Leopoldo A; Nahas, Willian C; Klatte, Tobias

    2016-01-01

    Bacillus Calmette-Guerin (BCG) is the standard of care for adjuvant intravesical instillation therapy for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection. Increasing evidence suggests that there are marked differences in outcomes according to BCG substrains. BCG-Moreau was recently introduced to the European market to cover the issue of BCG shortage, but there are little data regarding the oncologic efficacy. We retrospectively analyzed 295 consecutive patients, who received adjuvant intravesical instillation therapy with BCG-Moreau for intermediate- and high-risk NMIBC between October 2007 and April 2013 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. Median age was 66 years (interquartile range 59-74, mean 65.9 years). According to the EAU risk group, 76 patients presented with intermediate-risk and 219 patients with high-risk NMIBC. The 5-year recurrence-free survival and progression-free survival rate was 64.8% (95% CI 52.8-74.4) and 81.4% (95% CI 65.2-90.2), respectively. BCG-Moreau is an effective substrain for adjuvant instillation therapies of NMIBC, and outcomes appear to be comparable to series using other substrains. During worldwide shortage of BCG-TICE, Connaught and RIVM, BCG-Moreau may serve as an equally effective alternative. © 2015 S. Karger AG, Basel.

  17. Rodent malaria: BCG-induced protection and immunosuppression. [Mice, gamma radiation, Plasmodium berghei

    Energy Technology Data Exchange (ETDEWEB)

    Smrkovski, L.L.; Strickland, G.T.

    1978-10-01

    One dose of 10/sup 7/ viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10/sup 4/ thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge.

  18. Searching for the Recoiling Black Hole in BCG2261

    Science.gov (United States)

    Gultekin, Kayhan

    2017-09-01

    We propose a 100 ksec observation of the core of BCG 2261 to test for the presence of a recoiling SMBH. Binary SMBHs are thought to scour out cores in the host galaxy before coalescence of the black holes, which can lead to large recoils. Despite the importance of the connection between binary BHs, strong gravity, and galaxy evolution, it has never been conclusively observed. Without confirmation, we don't know if binary SMBHs can create stellar cores achieve high recoil velocities. We can produce the first direct observational proof of a recoiling SMBH in BCG 2261, the strongest candidate to date to host a recoiling SMBH and an extreme stellar core. With a detection, we will finally have definitive observational evidence connecting core formation, gravitational waves, and binary BHs.

  19. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Sílvia Bacalhau

    2011-01-01

    Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

  20. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    OpenAIRE

    Bacalhau, S; Freitas, C; Valente, R; Barata, D; Neves, C; Schäfer, K; Lubatschofski, A; Schulz, A; Farela Neves, J

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highligh...

  1. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment.

    Science.gov (United States)

    Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M; van de Sande, Paula J M; Whittle, Hilton; Fisker, Ane B; Roth, Adam; Aaby, Peter; Yazdanbakhsh, Maria; Benn, Christine S

    2010-05-21

    Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.

  2. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment.

    Directory of Open Access Journals (Sweden)

    Erliyani Sartono

    Full Text Available BACKGROUND: Oral polio vaccine (OPV is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW and normal-birth-weight (NBW infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. METHODS AND FINDINGS: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041 and IFN-gamma (p = 0.004 and a tendency for lower IL-10 (p = 0.054 in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR of having a PPD reaction being 0.75 (0.58-0.98, p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91-1.00, p = 0.057. Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05, p = 0.012. CONCLUSIONS: This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.

  3. Features of General Reactive Potential of the Body in Infants with BCG lymphadenitis

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    A.I. Bobrovitskaia

    2014-11-01

    Conclusions. When using BCG vaccine of Russian production, there is far less significant overload of blood flow by products of intoxication and inflammation, more pronounced body’s ability to respond to antigenic stimulus generalization and no risk of infection, especially in infants, compared with Danish BCG vaccine. For vaccination of infants against tuberculosis, it is advisable to use more refined, with high immunogenicity and less reactogenic BCG vaccine of Russian production. Despite the presence of complications when using BCG vaccine, protection of the body from the development of generalized forms of tuberculosis in young children is possible by vaccination in the neonatal period.

  4. Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

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    Leslie Chávez-Galán

    2016-01-01

    Full Text Available Mycobacterium bovis BCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports on M. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies.

  5. Active suppression of in vitro reactivity of spleen cells after BCG treatment

    International Nuclear Information System (INIS)

    Orbach-Arbouys, S.; Poupon, M.F.

    1978-01-01

    It was found that spleen cells from mice injected i.v. with large doses of BCG responded to PHA stimulation less intensely than did normal spleen cells. It was shown that nylon wool column purified BCG treated T cells also had a low PHA reactivity. Unfractionated spleen cells, adherent cells or T-enriched populations from BCG treated mice, when added to normal T cells lowered their PHA reactivity. When the same BCG treated cell populations were added to tumor cells in vitro, they inhibited their growth. (author)

  6. The immunological effects of oral polio vaccine provided with BCG vaccine at birth

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

    2014-01-01

    BACKGROUND: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based...... BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...

  7. Neonatal BCG vaccination influences cytokine responses to Toll-like receptor ligands and heterologous antigens.

    Science.gov (United States)

    Freyne, B; Donath, S; Germano, S; Gardiner, K; Casalaz, D; Robins-Browne, R M; Amenyogbe, N; Messina, N L; Netea, M G; Flanagan, K L; Kollmann, T; Curtis, N

    2018-02-03

    Bacille Calmette-Guérin (BCG) vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain but long-term modulation of the innate immune response (trained immunity) may be involved. Whole blood, collected 7 days post randomisation from 212 neonates enrolled in a randomised trial of neonatal BCG vaccination, was stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses. BCG-vaccinated infants had increased production of IL-6 in unstimulated samples and decreased production of IL-1ra, IL-6, and IL-10 and the chemokines MIP-1α, MIP-1β, MCP-1 following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8). BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternal BCG vaccination status interacted with neonatal BCG vaccination. Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effect is characterised by decreased anti-inflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstimulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is warranted to determine if there is an association between these findings and the beneficial non-specific (heterologous) effects of BCG vaccine on all-cause mortality.

  8. BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial.

    Directory of Open Access Journals (Sweden)

    Sérgio S Cunha

    2008-02-01

    Full Text Available Although BCG has been found to impart protection against leprosy in many populations, the utility of repeat or booster BCG vaccinations is still unclear. When a policy of giving a second BCG dose to school children in Brazil was introduced, a trial was conducted to assess its impact against tuberculosis, and a leprosy component was then undertaken in parallel.to estimate the protection against leprosy imparted by a second dose of BCG given to schoolchildren.This is a cluster randomised community trial, with 6 years and 8 months of follow-up.City of Manaus, Amazon region, a leprosy-endemic area in Brazil.99,770 school children with neonatal BCG (aged 7-14 years at baseline, of whom 42,662 were in the intervention arm (revaccination.BCG given by intradermal injection.Leprosy (all clinical forms.The incidence rate ratio of leprosy in the intervention over the control arm within the follow-up, in schoolchildren with neonatal BCG, controlled for potential confounders and adjusted for clustering, was 0.99 (95% confidence interval: 0.68 to 1.45.There was no evidence of protection conferred by the second dose of BCG vaccination in school children against leprosy during the trial follow-up. These results point to a need to consider the effectiveness of the current policy of BCG vaccination of contacts of leprosy cases in Brazilian Amazon region.

  9. Vacina BCG contra tuberculose: efeito protetor e políticas de vacinação BCG vaccine against tuberculosis: its protective effect and vaccination policies

    Directory of Open Access Journals (Sweden)

    Susan M Pereira

    2007-09-01

    Full Text Available OBJETIVO: A vacina BCG é utilizada desde 1921, embora ainda apresente controvérsias e aspectos não esclarecidos. O objetivo do artigo foi analisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e as políticas de vacinação adotadas. MÉTODOS: Foi realizada revisão sistemática da literatura publicada em inglês e espanhol, abrangendo o período compreendido entre 1948 e 2006, na base PubMed. Os principais descritores utilizados foram BCG vaccine, BCG efficacy, BCG e tuberculosis. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e metanálises. RESULTADOS: O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é elevado. No entanto, os resultados são discordantes em relação à forma pulmonar, variando de ausência de efeito a níveis próximos a 80%. Estão sendo conduzidas pesquisas sobre novas vacinas candidatas a substituir a BCG ou serem utilizadas como reforço. CONCLUSÕES: Há evidências de que a segunda dose da BCG não aumenta o seu efeito protetor. Apesar de seus limites e da expectativa futura de nova vacina para tuberculose, a vacina BCG mantém-se como importante instrumento no controle dos efeitos danosos da doença, sobretudo em países com taxas de incidência médias e elevadas.OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. METHODS: A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case

  10. Immune response elicited by two rBCG strains devoid of genes involved in c-di-GMP metabolism affect protection versus challenge with M. tuberculosis strains of different virulence.

    Science.gov (United States)

    Segura-Cerda, Cristian Alfredo; Aceves-Sánchez, Michel de Jesús; Marquina-Castillo, Brenda; Mata-Espinoza, Dulce; Barrios-Payán, Jorge; Vega-Domínguez, Perla Jazmín; Pedroza-Roldán, César; Bravo-Madrigal, Jorge; Vallejo-Cardona, Alba Adriana; Hernández-Pando, Rogelio; Flores-Valdez, Mario Alberto

    2018-04-12

    Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles. We found that deletion of the BCG1419c (Delta c-di-GMP phosphodiesterase, ΔPDE) gene, or deletion of the BCG1416c (Delta c-di-GMP diguanylate cyclase, ΔDGC) gene, altered production of TNF-α, IL-6, and IL-1β, in murine macrophages, and resulted in attenuation in intra-macrophage replication. Moreover, in addition to the improved immunogenicity of the BCGΔBCG1419c mutant already reported, deletion of the BCG1416c gene leads to increased T CD4 + and T CD8 + activation. This correlated with protection versus lethality in mice infected with the highly virulent M. tuberculosis 5186 afforded by vaccination with all the tested BCG strains, and controlled the growth of the mildly virulent M. tuberculosis H37Rv in lungs by vaccination with BCGΔBCG1419c during chronic late infection from 4 to 6 months after challenge. Furthermore, when grown as surface pellicles, a condition used to manufacture BCG vaccine, in comparison to BCG wild type, both rBCGs changed expression of antigenic proteins such as DnaK, HbhA, PstS2, 35KDa antigen, GroEL2, as well as AcpM, a protein involved in synthesis of mycolic acids, molecules relevant to modulate inflammatory responses. Copyright © 2018 Elsevier Ltd. All

  11. Production of BCG alginate-PLL microcapsules by emulsification/internal gelation.

    Science.gov (United States)

    Esquisabel, A; Hernández, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    1997-01-01

    A biocompatible emulsification method for microencapsulation of live cells and enzymes within a calcium alginate matrix applied to Bacillus Calmette-Guérin (BCG) has been developed. Small-diameter alginate beads (microcapsules) were formed via internal gelation of an alginate solution emulsified within vegetable oil. Five different oils (sesame, sweet almond, perhydrosqualene, camomile and jojoba) were used. The rheological analysis of the oils showed a Newtonian behaviour, with viscosities = 30.0, 37.7, 51.2, 59.3 and 67.1 mPa.s for perhydrosqualene, jojoba, camomile, sesame and sweet almond oil respectively. The particle size of the microcapsules obtained ranged from 30.3 microns for the microcapsules prepared with sweet almond oil to 57.0 microns for those made with perhydrosqualene. The mean particle diameter obtained was found to be dependent on the viscosity of the oil employed, according to the equation: phi (micron) = 76.6-0.628 eta (mPa.s) (r2 = 0.943). The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Freeze-drying of the microcapsules was carried out to ensure their stability during storage. Two batches of microcapsules (those prepared with sesame and jojoba oil) and four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol), at three concentration levels (5, 10 and 20% w/v) were studied. The parameters evaluated were particle size, physical appearance, reconstitution of lyophilizates and microscopical evaluation. For both batches of microcapsules the best results were obtained with trehalose 5%, showing particle sizes of 42.1 microns in the case of the microcapsules prepared with sesame oil, and of 45.3 microns for those prepared with jojoba.

  12. Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage

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    Bierrenbach Ana L.

    2003-01-01

    Full Text Available OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > 5 mm, > 10 mm, and > 15 mm and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > 15 mm. We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > 10 mm was 14.2% (95% confidence interval (CI = 8.0%-20.3% for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1% for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0% for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > 5 mm and > 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > 5 mm and > 10 mm did not vary with age. There was no evidence for BCG effect on the results > 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to

  13. Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG

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    Centola Michael

    2007-05-01

    Full Text Available Abstract Background Intravesical Bacillus Calmette-Guerin (BCG is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-α. We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder. Methods C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR was used to test whether intravesical BCG would alter bladder cytokine gene expression. Results Acute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-α treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1β, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and

  14. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.

    2010-01-01

    not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. Conclusions: This study is the first to address the consequences for the immune response to BCG of simultaneous administration...... only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p...

  15. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Directory of Open Access Journals (Sweden)

    Cyrill A Rentsch

    Full Text Available Intravesical Bacillus Calmette Guérin (BCG immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1 duration between resection and the first instillation; (2 BCG dose; (3 indwelling time; and (4 treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  16. Determinants of BCG scarification among children in rural Guinea-Bissau

    DEFF Research Database (Denmark)

    Funch, Katarina M; Thysen, Sanne M; Rodrigues, Amabelia

    2018-01-01

    : Bandim Health Project (BHP) runs a Health and Demographic Surveillance System site in rural Guinea-Bissau. BHP provides BCG at monthly visits. We studied determinants for not developing a BCG scar using binomial regression models to obtain relative risks (RR). RESULTS: From May 2012 until October 2014...

  17. IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

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    L. Amniai

    2007-01-01

    These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.

  18. Clinical manifestations of leprosy after BCG vaccination: An observational study in Bangladesh

    NARCIS (Netherlands)

    R. Richardus (Renate); C.R. Butlin (C. Ruth); K. Alam (Khorshed); K. Kundu (Kallyan); A. Geluk (Annemieke); J.H. Richardus (Jan Hendrik)

    2015-01-01

    textabstractBackground: Although BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy,

  19. Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in ...

    African Journals Online (AJOL)

    Aim. Bacille Calmette-Guérin (BCG) immunisation is well established as part of the South African national expanded programme for immunisation (EPI). The World Health Organization (WHO) currently recommends that BCG be given to all asymptomatic infants irrespective of HIV exposure at birth but does not recommend ...

  20. Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in ...

    African Journals Online (AJOL)

    Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in HIV infected children. J Karpelowsky, A Alexander, SD Peek, A Millar, H Rode. Abstract. Aim. Bacille Calmette-Guérin (BCG) immunisation is well established as part of the South African national expanded programme for immunisation (EPI). The World ...

  1. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.

    2010-01-01

    -up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus...

  2. Some characteristics of BCG-RIV lot no. 602, prepared to be used for immunostimulation in cancer therapy

    NARCIS (Netherlands)

    Steerenberg PA; de Jong WH; Kruizinga W; Ruitenberg EJ; Tiesjema RH; Kreeftenberg JG; Groothuis DG; Smid P; van Noorle Jansen LM

    1985-01-01

    In dit rapport worden verschillende eigenschappen van BCG batch 602, die gebruikt wordt voor immunotherapie bij kanker, onderzocht. Het bleek dat deze batch BCG dezelfde eigenschappen bezat als de voorafgaande BCG batches. Onderzocht werden de potentie van specifieke en a-specifieke

  3. Some characteristics of BCG-RIVM lot no. 605, prepared to be used for immunostimulation in cancer therapy

    NARCIS (Netherlands)

    Steerenberg PA; de Jong WH; Kruizinga W; Ruitenberg EJ; Tiesjema RH; Kreeftenberg JG; Groothuis DG; Smid P; van Noorle Jansen LM

    1986-01-01

    Het rapport behandelt de karakterisatie, toxiciteit en de effectiviteit van een nieuw geproduceerde batch BCG (BCG-RIVM, lot no. 605), bestemd voor immunotherapie bij de behandeling naar kanker. Uit dit onderzoek blijkt dat deze batch BCG dezelfde eigenschappen heeft als voorgaande

  4. Some characteristics of BCG-RIVM lot no 606, prepared to be used for immunostimulation in cancer therapy

    NARCIS (Netherlands)

    Steerenberg PA; de Jong WH; Kruizinga W; Ruitenberg EJ; Tiesjema RH; Kreeftenberg JG; Groothuis DG; Smid P; van Noorle Jansen LM

    1986-01-01

    Het rapport behandelt de karakterisatie, toxiciteit en de effectiviteit van een nieuw geproduceerde batch BCG (BCG-RIVM lot no. 606), bestemd voor immunotherapie bij de behandeling van kanker. Uit dit onderzoek blijkt dat deze batch BCG dezelfde eigenschappen heeft als voorgaande

  5. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2012-01-31

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  6. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2010-06-01

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  7. Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Lamosa Pedro

    2010-05-01

    Full Text Available Abstract Background Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127 was considered essential for growth, no mycobacterial Mak has, to date, been characterized. Results The sequence of the Mak from M. bovis BCG was identical to that from M. tuberculosis strains (99-100% amino acid identity. The enzyme was dependent on maltose and ATP, although GTP and UTP could be used to produce maltose-1-phosphate, which we identified by TLC and characterized by NMR. The Km for maltose was 2.52 ± 0.40 mM and 0.74 ± 0.12 mM for ATP; the Vmax was 21.05 ± 0.89 μmol/min.mg-1. Divalent cations were required for activity and Mg2+ was the best activator. The enzyme was a monomer in solution, had maximal activity at 60°C, between pH 7 and 9 (at 37°C and was unstable on ice and upon freeze/thawing. The addition of 50 mM NaCl markedly enhanced Mak stability. Conclusions The unknown role of maltokinases in mycobacterial metabolism and the lack of biochemical data led us to express the mak gene from M. bovis BCG for biochemical characterization. This is the first mycobacterial Mak to be characterized and its properties represent essential knowledge towards deeper understanding of mycobacterial physiology. Since Mak may be a potential drug target in M. tuberculosis, its high-level production and purification in bioactive form provide important tools for further functional and structural studies.

  8. Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

    2017-01-01

    Background. BCG vaccine may reduce overall mortality by increasing resistance to nontuberculosis infections. In 2 randomized trials in Guinea-Bissau of early BCG-Denmark (Statens Serum Institut) given to low-weight (LW) neonates (... ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0.......66; .44–1.00) when censoring for oral poliovirus vaccine campaigns. There was no reduction in mortality rate for noninfectious diseases, but a 43% reduction in infectious disease mortality rate (MRR, 0.57; 95% CI, .35–.93). A meta-analysis of 3 BCG trials showed that early BCG-Denmark reduced mortality...

  9. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960.

    Science.gov (United States)

    Brimnes, Niels

    2011-02-01

    Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.

  10. Neonatal BCG vaccination and atopic dermatitis before 13 months of age

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

    2018-01-01

    in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among......Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... age children in the BCG group and 495/1,952 (25.4%) children...

  11. Recombinant BCG vaccines: molecular features and their influence in the expression of foreign genes.

    Science.gov (United States)

    Oliveira, Thaís Larré; Rizzi, Caroline; Dellagostin, Odir Antônio

    2017-09-01

    Recombinant Mycobacterium bovis BCG vaccines (rBCG) were first developed in the 1990s as a means of expressing antigens from multiple pathogens. This review examines the key structural factors of recombinant M. bovis that influence the expression of the heterologous antigens and the generation of genetic and functional stability in rBCG, which are crucial for inducing strong and lasting immune responses. The fundamental aim of this paper is to provide an overview of factors that affect the expression of recombinant proteins in BCG and the generation of the immune response against the target antigens, including mycobacterial promoters, location of foreign antigens, and stability of the vectors. The reporter systems that have been employed for evaluation of these molecular features in BCG are also reviewed here.

  12. BCG-induced trained immunity in NK cells: Role for non-specific protection to infection.

    Science.gov (United States)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank; Joosten, Leo A B; Jacobs, Cor; Xavier, Ramnik J; van der Meer, Jos W M; van Crevel, Reinout; Netea, Mihai G

    2014-12-01

    Adaptive features of innate immunity, also termed 'trained immunity', have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination. BCG vaccination of healthy volunteers increased proinflammatory cytokine production following ex vivo stimulation of NK cells with mycobacteria and other unrelated pathogens up until at least three months after vaccination. In addition, in a murine model of disseminated candidiasis, BCG vaccination led to an increased survival in SCID mice, which was partially dependent on NK cells. These findings suggest that NK cells may contribute to the non-specific (heterologous) beneficial effects of BCG vaccination. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hermann Inge-Marie

    2010-06-01

    Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

  14. Pre-Clinical Development of BCG.HIVACAT, an Antibiotic-Free Selection Strain, for HIV-TB Pediatric Vaccine Vectored by Lysine Auxotroph of BCG

    Science.gov (United States)

    Saubi, Narcís; Mbewe-Mvula, Alice; Gea-Mallorqui, Ester; Rosario, Maximillian; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

    2012-01-01

    In the past, we proposed to develop a heterologous recombinant BCG prime-recombinant modified vaccinia virus Ankara (MVA) boost dual pediatric vaccine platform against transmission of breast milk HIV-1 and Mycobacterium tuberculosis (Mtb). In this study, we assembled an E. coli-mycobacterial shuttle plasmid pJH222.HIVACAT expressing HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism based on Operator-Repressor Titration (ORT) system for plasmid selection and maintenance in E. coli and lysine complementation in mycobacteria. This shuttle plasmid was electroporated into parental lysine auxotroph (safer) strain of BCG to generate vaccine BCG.HIVACAT. All procedures complied with Good Laboratory Practices (GLPs). We demonstrated that the episomal plasmid pJH222.HIVACAT was stable in vivo over a 20-week period, and genetically and phenotypically characterized the BCG.HIVACAT vaccine strain. The BCG.HIVACAT vaccine in combination with MVA.HIVA induced HIV-1- and Mtb-specific interferon γ-producing T-cell responses in newborn and adult BALB/c mice. On the other hand, when adult mice were primed with BCG.HIVACAT and boosted with MVA.HIVA.85A, HIV-1-specific CD8+ T-cells producing IFN-γ, TNF-α, IL-2 and CD107a were induced. To assess the biosafety profile of BCG.HIVACAT-MVA.HIVA regimen, body mass loss of newborn mice was monitored regularly throughout the vaccination experiment and no difference was observed between the vaccinated and naïve groups of animals. Thus, we demonstrated T-cell immunogenicity of a novel, safer, GLP-compatible BCG-vectored vaccine using prototype immunogen HIVA. Second generation immunogens derived from HIV-1 as well as other major pediatric pathogens can be constructed in a similar fashion to prime protective responses soon after birth. PMID:22927933

  15. Code system BCG for gamma-ray skyshine calculation

    International Nuclear Information System (INIS)

    Ryufuku, Hiroshi; Numakunai, Takao; Miyasaka, Shun-ichi; Minami, Kazuyoshi.

    1979-03-01

    A code system BCG has been developed for calculating conveniently and efficiently gamma-ray skyshine doses using the transport calculation codes ANISN and DOT and the point-kernel calculation codes G-33 and SPAN. To simplify the input forms to the system, the forms for these codes are unified, twelve geometric patterns are introduced to give material regions, and standard data are available as a library. To treat complex arrangements of source and shield, it is further possible to use successively the code such that the results from one code may be used as input data to the same or other code. (author)

  16. Sepse fatal após instilação intravesical de BCG: relato de caso Fatal sepsis after intravesical instillation of BCG: case report

    Directory of Open Access Journals (Sweden)

    Ulysses Vasconcellos de Andrade e Silva

    2011-03-01

    Full Text Available A instilação intravesical do bacilo de Calmette-Guérin (BCG é o tratamento de escolha para carcinoma de bexiga in situ ou tumores superficiais de bexiga de alto grau não invasivos. Este tratamento geralmente é bem tolerado, mas podem ocorrer complicações graves. Paciente idoso, coronariopata, portador de carcinoma superficial de bexiga de alto grau recidivado foi submetido à instilação intravesical de BCG, evoluindo com choque séptico. Recebeu antibioticoterapia de amplo espectro, tuberculostáticos, corticóide, aminas vasoativas, suporte ventilatório e tratamento hemodialítico, sem melhora. Faleceu nove dias após a instilação intravesical de BCG por insuficiência de múltiplos órgãos.Intravesical instillation of bacillus Calmette-Guérin (BCG is the treatment of choice for carcinoma in situ and non-invasive high-grade superficial tumors of the urinary bladder. This treatment is well tolerated overall, but serious complications can occur. An elderly man with coronary disease and recurrent high-grade superficial carcinoma of the bladder underwent intravesical instillation of BCG and developed septic shock. He received wide range antibiotics, tuberculostatic and vasoactive drugs, corticosteroids, mechanical ventilation and renal replacement therapy without improvement. He died nine days after the intravesical instillation of BCG because of multiple organ failure.

  17. Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

    Directory of Open Access Journals (Sweden)

    Ramos Kátia L

    2008-11-01

    Full Text Available Abstract Background Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-α and IL-10 expression and to evaluate antitumour activity. Methods For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF-〈 and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells. Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-α in the BCG-treated group, as well as increases in TNF-α and IL-10 mRNA in the rBCG-S1PT group. Conclusion These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-α and IL-10 cytokine productions may have therapeutic value.

  18. Collecting wrappers, labels, and packages to enhance accuracy of food records among children 2-8 years in the Pacific region: Children's Healthy Living Program (CHL).

    Science.gov (United States)

    Yonemori, Kim M; Ennis, Tui; Novotny, Rachel; Fialkowski, Marie K; Ettienne, Reynolette; Wilkens, Lynne R; Leon Guerrero, Rachael T; Bersamin, Andrea; Coleman, Patricia; Li, Fenfang; Boushey, Carol J

    2017-12-01

    The aim was to describe differences in dietary outcomes based on the provision of food wrappers, labels or packages (WLP) to complement data from dietary records (DR) among children from the US Affiliated Pacific. The WLP were intended to aid food coding. Since WLP can be associated with ultra-processed foods, one might expect differences in sodium, sugar, and other added ingredients to emerge. Dietary intakes of children (2-8 y) in Alaska, Hawai'i, Commonwealth of the Northern Mariana Islands, and Guam were collected using parent/caregiver completed 2-day DR. Parents were encouraged to collect WLP associated with the child's intake. Trained staff entered data from the DRs including the WLP when available using PacTrac3, a web application. Of the 1,868 DRs collected and entered at the time of this report, 498 (27%) included WLP. After adjusting for confounders (sex, age, location, education, food assistance), the DRs with WLP had significantly higher amounts of energy (kcal), total fat, saturated fat, added sugar, and sodium. These results suggest the inclusion of WLP enhanced the dietary intake data. The intake of energy, fat, added sugar and sodium derived from processed foods and foods consumed outside the home was better captured in children who had WLP.

  19. Vacuna contra la tuberculosis BCG: Eficacia y efectos adversos

    Directory of Open Access Journals (Sweden)

    Quezada-Andrade, Steven

    2015-12-01

    Full Text Available TB is the second leading cause of death from an infectious agent, disease caused by Mycobacterium tuberculosis. It allowed the creation of a vaccine officially launched in 1924 and known as Bacillus Calmette-Guerin (BCG used since then. However, there has been extensive research on its effectiveness and other related factors have shown an imbalance. Several countries recommend the use of this vaccine in infants, but in the case of Ecuador has failed to suggest its application, although there are no data regarding the efficacy of the vaccine in that country. Other studies show that the knowledge of people about the disease is destitute, thus allowing this could spread more quickly because the infected person does not know the type of symptoms that generates Tuberculosis. This article aims to identify the current status of the efficiency and safety of BCG through review and analysis of collected items related to the use of the vaccine and its effectiveness in the research population.

  20. Cosmological Constraints from the SDSS maxBCG Cluster Catalog

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /CCAPP; Wechsler, Risa H.; /KIPAC, Menlo Park /SLAC; Rykoff, Eli S.; /UC, Santa Barbara; Annis, James T.; /Fermilab; Becker, Matthew R.; /Chicago U. /KICP, Chicago; Evrard, August E.; /Michigan U. /Michigan U., MCTP; Frieman, Joshua A.; /Fermilab /KICP, Chicago /Chicago U.; Hansen, Sarah M.; /UC, Santa Cruz; Hao, Jia; /Michigan U.; Johnston, David E.; /Northwestern U.; Koester, Benjamin P.; /KICP, Chicago /Chicago U.; McKay, Timothy A.; /Michigan U. /Michigan U., MCTP; Sheldon, Erin S.; /Brookhaven; Weinberg, David H.; /CCAPP /Ohio State U.

    2009-08-03

    We use the abundance and weak lensing mass measurements of the SDSS maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat {Lambda}CDM cosmology, we find {sigma}{sub 8}({Omega}{sub m}/0.25){sup 0.41} = 0.832 {+-} 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find {sigma}{sub 8} = 0.807 {+-} 0.020 and {Omega}{sub m} = 0.265 {+-} 0.016, an improvement of nearly a factor of two relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically-selected cluster samples to produce precision constraints on cosmological parameters.

  1. Preparation and stability of agarose microcapsules containing BCG.

    Science.gov (United States)

    Esquisabel, A; Hernandez, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    2002-01-01

    An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guerin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 microm for the microcapsules prepared with sweet almonds oil to 42.6 microm for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.

  2. Early BCG vaccine to low-birth-weight infants and the effects on growth in the first year of life

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Andersen, Andreas; Ravn, Henrik

    2015-01-01

    BACKGROUND: Randomised trials have shown that early Bacille Calmette-Guérin (BCG) vaccine reduces overall neonatal and infant mortality. However, no study has examined how BCG affects growth. We investigated the effect on infant growth of early BCG vaccine given to low-birth-weight (LBW) infants...... A supplementation (VAS) or placebo. Anthropometric measurements were obtained 2, 6, and 12 months after enrolment. RESULTS: Overall there was no effect of early BCG on growth in the first year of life. The effect of early BCG on weight and mid-upper-arm circumference at 2 months tended to be beneficial among girls...... but not among boys (interaction between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial effect among girls was particularly seen among the largest infants weighing 2.0 kg or more at inclusion. CONCLUSION: Though BCG vaccination is not recommended to be given to LBW infants at birth...

  3. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants

    DEFF Research Database (Denmark)

    Nørrelykke Nissen, Thomas; Birk, Nina Marie; Kjærgaard, Jesper

    2016-01-01

    OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG...... and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. MAIN OUTCOME AND MEASURE: Trial-registered adverse reactions after BCG...... vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. RESULTS: Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional...

  4. MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Frank A W Verreck

    Full Text Available Continuous high global tuberculosis (TB mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection.Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A, and attenuated M. tuberculosis with a disrupted phoP gene (SO2 as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60.Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates.

  5. Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

    Directory of Open Access Journals (Sweden)

    MohammadReza Rafati

    2015-10-01

    Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

  6. Vaccination with a BCG strain overexpressing Ag85B protects cattle against Mycobacterium bovis challenge.

    Directory of Open Access Journals (Sweden)

    Caroline Rizzi

    Full Text Available Mycobacterium bovis is the causative agent of tuberculosis in cattle but also infects other animals, including humans. Previous studies in cattle have demonstrated that the protection induced by BCG is not complete. In order to improve the protection efficacy of BCG, in this study we overexpressed Ag85B in a BCG Pasteur strain, by using an expression system based on the use of an auxotrophic strain for the leucine amino acid, and complementation with leuD. We found that vaccination of cattle with BCG overexpressing Ag85B induced higher production of IL-17 and IL-4 mRNA upon purified protein derivative (PPDB stimulation of peripheral blood mononuclear cells (PBMCs than vaccination with BCG. Moreover, the IL-17 mRNA expression after vaccination negatively correlated with disease severity resulting from a subsequent challenge with M. bovis, suggesting that this cytokine is a potential biomarker of cattle protection against bovine tuberculosis. Importantly, vaccination with the recombinant BCG vaccine protected cattle better than the wild-type BCG Pasteur.

  7. BCG-associated heterologous immunity, a historical perspective: experimental models and immunological mechanisms.

    Science.gov (United States)

    Freyne, Bridget; Marchant, Arnaud; Curtis, Nigel

    2015-01-01

    Randomized controlled trials indicate that bacille Calmette-Guerin (BCG) has beneficial heterologous ('non-specific') effects on mortality in high mortality settings. These findings have stimulated interest in understanding the immunological mechanisms underlying these effects in the hope of harnessing them to reduce all-cause mortality. This line of investigation is especially important in light of BCG being discontinued in some countries as the prevalence of TB falls. Stopping routine BCG in this situation may have the unintended consequence of depriving children of the beneficial immune modulating effects of this vaccine. BCG has been recognized as a potent immunomodulator for decades. This review details experimental studies involving BCG and any heterologous antigen that aimed to interrogate potential immunological mechanisms. To provide a historical perspective, the evidence is presented chronologically. The lines of immunological enquiry can be seen to mirror the evolution of our understanding of cell-mediated immunity and its components. As new clinical trials to investigate the heterologous effects of BCG are undertaken, an understanding of the history of BCG-induced immunity against heterologous antigens may provide information on immunological pathways worthy of further interrogation using modern immunological methods. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy

    Science.gov (United States)

    Minassian, Angela M.; Ronan, Edward O.; Poyntz, Hazel; Hill, Adrian V. S.; McShane, Helen

    2011-01-01

    There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection. PMID:21629699

  9. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau.

    Science.gov (United States)

    Roth, Adam Edvin; Benn, Christine Stabell; Ravn, Henrik; Rodrigues, Amabelia; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Aaby, Peter

    2010-03-15

    To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Randomised trial, with follow-up to age 5. A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants. 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrollment. BCG vaccination or no vaccination (control). Hazard ratios for mortality. 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrollment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrollment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrollment (1.78, 1.04 to 3.04). There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions. Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.

  10. Modification of death rate of irradiated mice by B.C.G

    International Nuclear Information System (INIS)

    Allain, P.; Chaleil, D.; Maingot, D.; Larra, F.

    1976-01-01

    Freeze-dried Bacillus Calmette Guerin (BCG) of Institut Pasteur was given by intravenous route to mice at 1,2 and 4mg/kg before and after γ irradiation of animals by 1000 rad. B.C.G. 1 mg/kg injected the day or the day after irradiation has a protective effect (mortality reduced from 77% for controls to 58% and 50% for treated mice). B.C.G. given before irradiation in single or double doses increased mortality [fr

  11. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma. [Hard X Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pines, A.

    1980-08-01

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient.

  12. Co-administration of BCG and Diphtheria-tetanus-pertussis (DTP) Vaccinations May Reduce Infant Mortality More Than the WHO-schedule of BCG First and Then DTP. A Re-analysis of Demographic Surveillance Data From Rural Bangladesh.

    Science.gov (United States)

    Aaby, Peter; Andersen, Andreas; Ravn, Henrik; Zaman, K

    2017-08-01

    WHO recommends BCG at birth and diphtheria-tetanus-pertussis (DTP)-containing vaccine at 6, 10 and 14weeks of age. However, BCG and DTP are often co-administered in low-income countries. The health implications have not been examined. We reanalysed data from Matlab, Bangladesh, to examine the influence of co-administration on mortality; 37,894 children born 1986-1999 were followed with registration of vaccinations and survival. Using Cox models, survival was analysed from 6weeks to 9months of age when measles vaccine is given; 712 children died in this age group. We calculated mortality rate ratios (MRR) for children starting the vaccination schedule with BCG-first, BCG+DTP1-first or DTP1-first. Only 17% followed the WHO-schedule with BCG-first. Mortality was 16/1000 person-years for children who initiated the vaccination schedule with BCG+DTP1 but 32/1000 and 20/1000 for children who received BCG-first or DTP-first, respectively. Compared with BCG+DTP1-first and adjusting for background factors, the BCG-first-schedule was associated with 2-fold higher mortality (MRR=1.94 (1.42-2.63)). DTP1 administered after BCG-first was associated with higher mortality than receiving DTP1 with BCG (MRR=1.78 (1.03-3.03)). Co-administration of BCG and DTP may further reduce mortality. Since all observational studies support this trend, co-administration of BCG and DTP should be tested in randomised trials. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Vaccination against M. tuberculosis – what next after BCG?

    Directory of Open Access Journals (Sweden)

    Marek Fol

    2011-01-01

    Full Text Available Tuberculosis (TB still remains a huge global health problem. An increase in TB has been observed in many parts of the world, especially in poor and densely populated sub-Saharan Africa and Asia. Tuberculosis affects not only the developing countries but also the relatively wealthy regions of Europe, particularly Eastern Europe, where drug-resistant mycobacterial strains are increasingly reported.Control of tuberculosis expansion is very difficult. It requires the long-term use of anti-mycobacterial drugs. Additionally, the HIV epidemic and the phenomenon of multi-drug resistance are assumed to be responsible for the increase in TB cases. Therefore the most reasonable form of anti-TB protection seems to be effective vaccination.At the beginning of the twentieth century the BCG vaccine was introduced into general use as the first and so far the only immune protector against tuberculosis. Now it is known that this vaccine is not powerful enough and induces protection at a relatively low level. Hence ongoing research on the development of a more powerful anti-mycobacterial vaccine is still needed. Many of the new formulations are in phase II or III of clinical trials and the results are promising. The search for new vaccines involves several strategies: modified virulence-attenuated [i]Mycobacterium tuberculosis[/i] strains, recombination of attenuated M. bovis BCG bacilli, immunogenic mycobacterial proteins and DNA encoding selected proteins as well as unrelated microorganisms used as carriers of mycobacterial antigens. The wide range of concepts is extremely important because new vaccines should serve for immunization of the broadest possible population, not only healthy individuals but also those who are immunocompromised.

  14. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.

    2010-01-01

    Objective To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Design Randomised trial, with follow-up to age 5. Setting A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000...... ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrolment (1.78, 1.04 to 3.04). Conclusions There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions...... children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...

  15. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna

    2010-01-01

    OBJECTIVE: To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. DESIGN: Randomised, placebo controlled, two by two factorial trial. SETTING: Bissau, Guinea-Bissau. PARTICIPANTS: 1717 low birthweight neonates born at the national hospital...... months of age for infants who received vitamin A supplementation compared with those who received placebo. RESULTS: No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality......: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation...

  16. Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A randomised clinical trial

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

    2017-01-01

    Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...

  17. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood

    DEFF Research Database (Denmark)

    Kiraly, N; Benn, Christine Stabell; Biering-Sørensen, S

    2013-01-01

    Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood....

  18. Using BCG as a framework for setting goals and communicating progress toward those goals

    Science.gov (United States)

    This 5 minute Lightning Talk will discuss the benefits of stakeholder-supported quantitative targets in measuring progress, and will describe the Biological Condition Gradient (BCG) as one way to develop these quantitative targets.

  19. Failure of bacillus calmette guerin (bcg) therapy for the treatment of ...

    African Journals Online (AJOL)

    BCG) instillation following complete transurethral resection of superficial transitional cell carcinoma (TCC) of the urinary bladder at the Urology Department, Al-Azhar University, Cairo, Egypt. Patients and Methods: A prospective analysis of 160 ...

  20. Mycobacterium bovis BCG promotes tumor cell survival from tumor necrosis factor-α-induced apoptosis.

    Science.gov (United States)

    Holla, Sahana; Ghorpade, Devram Sampat; Singh, Vikas; Bansal, Kushagra; Balaji, Kithiganahalli Narayanaswamy

    2014-09-11

    Increased incidence of lung cancer among pulmonary tuberculosis patients suggests mycobacteria-induced tumorigenic response in the host. The alveolar epithelial cells, candidate cells that form lung adenocarcinoma, constitute a niche for mycobacterial replication and infection. We thus explored the possible mechanism of M. bovis Bacillus Calmette-Guérin (BCG)-assisted tumorigenicity in type II epithelial cells, human lung adenocarcinoma A549 and other cancer cells. Cancer cell lines originating from lung, colon, bladder, liver, breast, skin and cervix were treated with tumor necrosis factor (TNF)-α in presence or absence of BCG infection. p53, COP1 and sonic hedgehog (SHH) signaling markers were determined by immunoblotting and luciferase assays, and quantitative real time PCR was done for p53-responsive pro-apoptotic genes and SHH signaling markers. MTT assays and Annexin V staining were utilized to study apoptosis. Gain- and loss-of-function approaches were used to investigate the role for SHH and COP1 signaling during apoptosis. A549 xenografted mice were used to validate the contribution of BCG during TNF-α treatment. Here, we show that BCG inhibits TNF-α-mediated apoptosis in A549 cells via downregulation of p53 expression. Substantiating this observation, BCG rescued A549 xenografts from TNF-α-mediated tumor clearance in nude mice. Furthermore, activation of SHH signaling by BCG induced the expression of an E3 ubiquitin ligase, COP1. SHH-driven COP1 targeted p53, thereby facilitating downregulation of p53-responsive pro-apoptotic genes and inhibition of apoptosis. Similar effects of BCG could be shown for HCT116, T24, MNT-1, HepG2 and HELA cells but not for HCT116 p53(-/-) and MDA-MB-231 cells. Our results not only highlight possible explanations for the coexistence of pulmonary tuberculosis and lung cancer but also address probable reasons for failure of BCG immunotherapy of cancers.

  1. Reiter’s syndrome occurred following intravesical BCG immunotherapy: Case presentation

    Directory of Open Access Journals (Sweden)

    Fatih Elbir

    2015-06-01

    Full Text Available Intravesical instillation of Bacillus Calmette Guerin (BCG is used in the treatment of patients with superficial bladder carcinoma with efficacy and safety. Although clinically very effective this method is associated with a variety of side effects. In these side effects, Reiter’s Syndrome is occurred most rare. We report here the case of Reiter’s Syndrome following BCG instillation with a different clinical manifestation.

  2. Mycobacterium bovis BCG: the importance of an accurate identification in the diagnostic routine

    Directory of Open Access Journals (Sweden)

    Antonella Grottola

    2010-09-01

    Full Text Available M. bovis BCG is used clinically in the immunotherapy treatment of superficial bladder cancer to prevent progression to invasive disease, leading in some cases to a severe localized inflammation or disseminated infections. For this reason, an accurate and early identification of this particular microorganism is clinically relevant.We describe a case-report of bladder cancer with a urine culture-positive for mycobacteria initially diagnosed as MTB complex infection and later identified as BCG disease by molecular methods.

  3. Removal of BCG artefact from concurrent fMRI-EEG recordings based on EMD and PCA.

    Science.gov (United States)

    Javed, Ehtasham; Faye, Ibrahima; Malik, Aamir Saeed; Abdullah, Jafri Malin

    2017-11-01

    Simultaneous electroencephalography (EEG) and functional magnetic resonance image (fMRI) acquisitions provide better insight into brain dynamics. Some artefacts due to simultaneous acquisition pose a threat to the quality of the data. One such problematic artefact is the ballistocardiogram (BCG) artefact. We developed a hybrid algorithm that combines features of empirical mode decomposition (EMD) with principal component analysis (PCA) to reduce the BCG artefact. The algorithm does not require extra electrocardiogram (ECG) or electrooculogram (EOG) recordings to extract the BCG artefact. The method was tested with both simulated and real EEG data of 11 participants. From the simulated data, the similarity index between the extracted BCG and the simulated BCG showed the effectiveness of the proposed method in BCG removal. On the other hand, real data were recorded with two conditions, i.e. resting state (eyes closed dataset) and task influenced (event-related potentials (ERPs) dataset). Using qualitative (visual inspection) and quantitative (similarity index, improved normalized power spectrum (INPS) ratio, power spectrum, sample entropy (SE)) evaluation parameters, the assessment results showed that the proposed method can efficiently reduce the BCG artefact while preserving the neuronal signals. Compared with conventional methods, namely, average artefact subtraction (AAS), optimal basis set (OBS) and combined independent component analysis and principal component analysis (ICA-PCA), the statistical analyses of the results showed that the proposed method has better performance, and the differences were significant for all quantitative parameters except for the power and sample entropy. The proposed method does not require any reference signal, prior information or assumption to extract the BCG artefact. It will be very useful in circumstances where the reference signal is not available. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.

    Science.gov (United States)

    Bizzell, Erica; Sia, Jonathan Kevin; Quezada, Melanie; Enriquez, Ana; Georgieva, Maria; Rengarajan, Jyothi

    2017-12-28

    Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine strain Mycobacterium bovis Bacille Calmette-Guérin (BCG) shares many of the immune evasion proteins utilized by Mtb, but the role of these proteins in DC and T cell responses elicited by BCG is poorly understood. We previously reported that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during infection. Here, we tested the hypothesis that BCG Hip1 modulates DC functions and prevents optimal antigen-specific CD4 T cell responses that limit the immunogenicity of BCG. We generated a strain of BCG lacking hip1 (BCGΔhip1) and show that it has superior capacity to induce DC maturation and cytokine production compared with the parental BCG. Furthermore, BCGΔhip1-infected DCs were more effective at driving the production of IFN-γ and IL-17 from antigen-specific CD4 T cells in vitro. Mucosal transfer of BCGΔhip1-infected DCs into mouse lungs induced robust CD4 T cell activation in vivo and generated antigen-specific polyfunctional CD4 T cell responses in the lungs. Importantly, BCGΔhip1-infected DCs enhanced control of pulmonary bacterial burden following Mtb aerosol challenge compared with the transfer of BCG-infected DCs. These results reveal that BCG employs Hip1 to impair DC activation, leading to attenuated lung CD4 T cell responses with limited capacity to control Mtb burden after challenge. ©2017 Society for Leukocyte Biology.

  5. The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marcela Henao-Tamayo

    Full Text Available To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.

  6. Murine Splenic Natural Killer Cells Do Not Develop Immunological Memory after Re-Encounter with Mycobacterium bovis BCG

    Science.gov (United States)

    Kawahara, Mamoru; Hasegawa, Nozomi; Takaku, Hiroshi

    2016-01-01

    Several lines of evidence have recently suggested that natural killer (NK) cells develop immunological memory against viral infections. However, there is no apparent evidence that NK cells acquire specific memory against Mycobacterium bovis bacillus Calmette—Guérin (BCG), the only currently licensed vaccine for preventing tuberculosis. In the present study, we investigated whether murine splenic NK cells can be activated by BCG in a dendritic cell (DC)-independent or -dependent manner, and furthermore examined whether these NK cells acquire specific memory following BCG vaccination. NK cells isolated from spleens of BCG-immunized mice produced interferon (IFN)γ through direct BCG stimulation in the absence of antigen-presenting cells; however, NK cells from control animals similarly directly responded to BCG, and the response level was not statistically significant between the immunized and the naïve NK cells. When purified NK cells that had been exposed to BCG were cocultured with RAW murine macrophages infected with BCG, the antibacterial activity of the macrophages was strongly enhanced; however, its level was similar to that by naïve NK cells, which had not been exposed to BCG. When splenocytes harvested from BCG-immunized mice were stimulated with purified protein derivative (PPD) derived from Mycobacterium tuberculosis, a specific IFNγ response was clearly observed, mainly attributed to NK cells and memory CD4+ T cells. To investigate whether these NK cells as well as the T cells are activated by cell−cell interaction with DCs presenting mycobacterial antigens, NK cells isolated from BCG-immunized mice were cocultured with splenocytes harvested from naïve mice in the presence of PPD stimulation. However, no IFNγ response was found in the NK cells. These results suggest that murine splenic NK cells do not develop BCG-specific immunological memory in either a DC-independent or -dependent manner. PMID:26999357

  7. Characterization of inflammasome-related genes in urine sediments of patients receiving intravesical BCG therapy.

    Science.gov (United States)

    Poli, Giulia; Cochetti, Giovanni; Boni, Andrea; Egidi, Maria Giulia; Brancorsini, Stefano; Mearini, Ettore

    2017-12-01

    Nowadays, the intravesical Bacillus Calmette-Guérin (BCG) instillation is the method of choice for the postsurgical treatment of high-grade nonmuscle-invasive bladder cancer , to reduce both recurrence rate and risk of progression. BCG is hypothesized to correct the immune system disequilibrium occurring during carcinogenesis, through an immunostimulation with detrimental effects for tumoral cells. Inflammation plays a crucial role in tumor progression. The deregulation of inflammasomes upon carcinogenesis underlines its importance both in physiologic and pathologic human conditions. Nucleotide oligomerization domain-like receptors (NLRs) are key components of this molecular platform and the increase in expression of some members of nucleotide oligomerization domain-like receptors family (NLRP3, NLRP4, NLRP9, and NLR family apoptosis inhibitory protein [NAIP]) in urothelial carcinoma was already demonstrated in our previous work. The first aim of the present work was to estimate whether these inflammasome-related genes show alterations during BCG instillations. The expression levels of NLRP3, NLRP4, NLRP9, and NAIP were assessed in the urine sediments from patients, which underwent surgery for superficial high-grade bladder cancer and further subjected to serial BCG instillations. The eventual association between NLR expression and recurrence was also evaluated. The expression of CK20 mRNA as confirmed marker of bladder cancer was also assayed. Urine were sampled from patients harboring high-grade superficial bladder cancer and treated postsurgically with weekly BCG instillations for 6 weeks (induction cycle, I). Urine sediments were processed and resulting RNA was reverse transcribed and used for amplification by real-time PCR. After surgery, CK20 levels decreased significantly whereas NLRP4 and NLRP9 genes showed an increase. NLRP3 and NAIP remained substantially unmodified. CK20 mRNA decreased at the end of the induction cycle. NLRP3 did not show relevant

  8. Rapid Protective Effects of Early BCG on Neonatal Mortality Among Low Birth Weight Boys: Observations From Randomized Trials.

    Science.gov (United States)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Monterio, Ivan; Ravn, Henrik; Aaby, Peter; Benn, Christine Stabell

    2018-02-14

    Three randomized trials (RCTs) in low-weight (BCG) vaccine nonspecifically reduces all-cause mortality in the neonatal period. Using data from 3 RCTs of early BCG (n = 6583) we examined potential sex differences in the timing of the mortality reduction in the neonatal period, presenting metaestimates of the main outcome mortality rate ratios (MRR) for BCG-vaccinated and controls. Among controls, boys had a particularly high mortality during the first week after randomization: male-female MRR 2.71 (95% CI, 1.70-4.50). During the first week, BCG had a marked beneficial effect for boys, reducing mortality 3-fold (MRR [BCG/no BCG] = 0.36 [0.20-0.67]). In weeks 2-4 the effect waned for boys (MRR = 0.91 [0.51-1.69]). In girls, the pattern was opposite with a limited effect in the first week (MRR = 0.85 [0.46-1.54]), but a significant reduction in weeks 2-4 (MRR = 0.56 [0.31-1.00]). This was consistent in all 3 trials. Verbal autopsies linked early benefit to fewer sepsis-related deaths among BCG-vaccinated boys. The marked reduction in mortality in the days after BCG vaccination in boys emphasizes the importance of providing BCG soon after birth. ClinicalTrials.gov (NCT00146302) and ClinicalTrials.gov (NCT00625482).

  9. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?

    Science.gov (United States)

    Aaby, Peter; Roth, Adam; Ravn, Henrik; Napirna, Bitiguida Mutna; Rodrigues, Amabelia; Lisse, Ida Maria; Stensballe, Lone; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Biering-Sørensen, Sofie; Whittle, Hilton; Benn, Christine Stabell

    2011-07-15

    Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children. Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63-1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21-1.15) after 3 days and .55 (.34-.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing <1.5 kg (MRR = .43 [.21-.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations. Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.

  10. Natural course of asymptomatic abnormal prostate findings incidentally detected by CT after intravesical BCG therapy.

    Science.gov (United States)

    Matsushima, Masashi; Kikuchi, Eiji; Akita, Hirotaka; Miyajima, Akira; Oya, Mototsugu; Jinzaki, Masahiro

    2017-06-01

    Detailed information is not currently available on the incidence, natural course, and management of asymptomatic abnormal prostate findings incidentally detected by radiologic evaluations after BCG therapy for non-muscle-invasive bladder cancer patients. We identified 38 patients who were evaluated by contrast-enhanced CT scans before TUR-BT and after BCG therapy between 2006 and 2012. We evaluated the clinical courses of patients with abnormal radiologic findings of the prostate gland after BCG therapy. Abnormal findings on CT scans were found in the prostate glands of 11 of the 38 patients examined (28.9%), none of whom exhibited any sign or symptom associated with prostatitis. Abnormal findings included a low attenuation area (n = 6, 15.8%), contrast enhancement (n = 3, 7.9%), and a low attenuation area and contrast enhancement in the prostate gland (n = 2, 5.3%). During the follow-up, abnormal prostate findings disappeared spontaneously in most cases without any anti-bacterial or anti-tuberculous drug treatments. No significant differences were observed in patient clinical backgrounds, with the exception of post-BCG prostate volumes, between patients with and without abnormal CT findings. Furthermore, no significant differences were noted in the incidence of the adverse effects of BCG therapy, tumor recurrence rates, or progression rates between patients with and without abnormal CT findings of the prostate gland after BCG therapy. Asymptomatic abnormal prostate findings incidentally detected by CT after BCG therapy are not rare, and these disappear over time during the follow-up period without any treatment.

  11. Erythema at BCG Inoculation Site in Kawasaki Disease Patients.

    Science.gov (United States)

    Rezai, Mohammad Sadegh; Shahmohammadi, Soheila

    2014-08-01

    Kawasaki disease is an acute, self-limiting childhood systemic vasculitis with unknown etiology. Because there is no diagnostic test for Kawasaki disease, the diagnosis is based on clinical criteria. An important clinical sign that is not included in the classical clinical criteria for Kawasaki disease is a reaction at the Bacille Calmette-Guérin inoculation site that are present in about 30-50% of Kawasaki disease patients. of this review was to highlight the usefulness of the inflammation at the Bacille Calmette-Guérin inoculation site for early diagnosis of Kawasaki disease, we conducted a literature review on Medline in PubMed area, Google scholar, Magiran and Scientific Information Database using the search terms "Kawasaki disease, Erythema, BCG, inoculation site, children, cardiac complications, coronary artery lesion, aneurysm, incomplete Kawasaki in 2013. A total of 15 articles had been found. Erythema at the Bacille Calmette-Guérin inoculation site was found in 49.87% of Kawasaki disease patients. Coronary artery abnormalities were found in 10.3% of cases. According to this review, BCGitis is more prevalent than cervical lymphadenopathy and rash and it can be a useful criterion in the diagnosis of incomplete Kawasaki disease in cases not fulfills the classic criteria of at least four of the five findings.

  12. Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.

    Science.gov (United States)

    Biet, F; Duez, C; Kremer, L; Marquillies, P; Amniai, L; Tonnel, A-B; Locht, C; Pestel, J

    2005-08-01

    Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12. We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction. Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG. A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups. These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

  13. Maternal BCG scar is associated with increased infant proinflammatory immune responses.

    Science.gov (United States)

    Mawa, Patrice Akusa; Webb, Emily L; Filali-Mouhim, Abdelali; Nkurunungi, Gyaviira; Sekaly, Rafick-Pierre; Lule, Swaib Abubaker; Prentice, Sarah; Nash, Stephen; Dockrell, Hazel M; Elliott, Alison M; Cose, Stephen

    2017-01-05

    Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other's effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray. Maternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus -0.94 in scar-negative, p=0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Maternal BCG scar had a stronger association with infant

  14. BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial.

    Science.gov (United States)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter; Benn, Christine Stabell; Greisen, Gorm; Jeppesen, Dorthe Lisbeth; Birk, Nina Marie; Kjærgaard, Jesper; Nissen, Thomas Nørrelykke; Pihl, Gitte Thybo; Thøstesen, Lisbeth Marianne; Kofoed, Poul-Erik; Pryds, Ole; Ravn, Henrik

    2017-03-01

    The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population. NCT01694108, results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Recombinant HBHA Boosting Effect on BCG-Induced Immunity against Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    G. G. Guerrero

    2011-01-01

    Full Text Available Heterologous prime-boost regimens are effective strategies to promote long-term memory and strong cellular Th1 responses to Mycobacterium tuberculosis, when BCG is used in the priming step. Subcutaneous or intranasal boosting of BCG-vaccinated newborn mice with native heparin-binding haemagglutinin (nHBHA significantly enhances protection against M. tuberculosis. However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination. In this study we addressed the question whether boosting with recombinant, non-methylated HBHA (rHBHA produced in Escherichia coli may enhance protection of BCG-primed newborn mice. We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; P<0.05 but not in the lungs. Thus, in BCG-primed mice the methylation of the C-terminal domain of HBHA is dispensable for the induction of enhanced protection in the lungs against intranasal but not aerosol infection, whereas it enhances protection in the spleen in both challenge models. This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.

  16. Clinical features and outcome of eleven patients with disseminated Bacille Calmette-Guerin (BCG) infection

    International Nuclear Information System (INIS)

    Al-Arishi, Haider M.; Frayha, Husn H.; Qari, Hussni Y.; Al-Rayes, H.; Tufenkeji, Haysam T.; Harfi, H.

    1996-01-01

    Disseminated BCG infection is a very rare complication of BCG vaccination. This study presents 11 patients with such complication. The underlying disease in eight of the 11 patients was primary immunodeficiency. Seven of these had severe combined immune deficiency (SCID) and one had isolated T-cell defect. Of the three remaining patients, one was healthy, one was diagnosed with mucocutaneous candidiasis and the third was diagnosed with leukocytoclastic vasculitis. Cutaneous nodular lesion, persistent fever, hepatosplenomegaly and pulmonary symptoms were common presenting features. All but one patient received antituberculous treatment. Four of 11 patients died because of extensive BCG disease. Three of these had SCID and one had T-cell deficiency. Patients with SCID who survived had bone marrow transplantation in addition to antituberculous chemotherapy. We conclude that a family history of immunodeficiency should be sought and if suggestive, BCG vaccine should be deferred until the immune status of the baby is clarified. In addition, early diagnosis is important for successful outcome. Bone marrow transplant on an emergency basis is the treatment of choice in patients with SCID and disseminated BCG infection, as immune reconstitution is essential to control infection in these patients. (author)

  17. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    Science.gov (United States)

    Singh, Sarman; Singh, Pragati

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine. PMID:25694828

  18. H2O2 generation by BCG induces the cellular oxidative stress response required for BCG’s direct effects on urothelial carcinoma tumor biology

    Science.gov (United States)

    Shah, Gopitkumar; Zielonka, Jacek; Chen, Fanghong; Zhang, Guangjian; Cao, YanLi; Kalyanaraman, Balaraman; See, William

    2018-01-01

    INTRODUCTION Exposure of urothelial carcinoma (UC) cells to Bacille Calmette Guerin (BCG) affects cellular redox status and tumor cell biology but mechanism(s) remains unclear. This study examined free radical production by BCG, and in tumor cells in response to BCG, using global profiling of Reactive oxygen species/reactive nitrogen species (ROS/RNS). The relationship between free radical generation and downstream cellular events was evaluated. MATERIALS AND METHODS Using fluorescent probes, global profiling of ROS/RNS was carried out in Heat killed (hk) BCG, viable BCG, and in two UC cell lines post BCG exposure (253J and T24). Inhibition of BCG internalization and pharmacologic scavenging of H2O2 was studied for their effect on cellular ROS/RNS generation and various physiological end points. RESULTS Viable BCG produced H2O2 (Hydrogen peroxide) and O2− (Superoxides) but did not show NO (Nitric oxide) generation. Loss of viability decreased production of H2O2 by 50% compared to viable BCG. BCG internalization was necessary for BCG induced ROS/RNS generation in UC cells. Pharmacologic H2O2 scavenging reversed the ROS/RNS mediated signaling in UC cells. BCG dependent alterations in tumor biology including intracellular signaling, gene expression and cytotoxicity were dependent on free radical generation. CONCLUSIONS This study demonstrates the importance of free radical generation by BCG, and intracellular generation of Cellular oxidative stress (COS), on the UC cell response to BCG. Manipulation of the BCG induced COS represents a potential target for increasing BCG efficacy. PMID:24928267

  19. Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status.

    Science.gov (United States)

    Rhodes, Sophie J; Knight, Gwenan M; Fielding, Katherine; Scriba, Thomas J; Pathan, Ansar A; McShane, Helen; Fletcher, Helen; White, Richard G

    2016-01-01

    A more effective tuberculosis (TB) vaccine is needed to eliminate TB disease. Many new vaccine candidates enhance the immunogenicity of the existing vaccine, Bacillus Calmette-Guérin (BCG). Understanding BCG induced immune variation is key to developing a new vaccine. We aimed to establish if individual-level covariates were associated with cell-mediated immune response (interferon gamma (IFN-γ)) at vaccine trial enrolment (baseline) in a long-term retrospective analysis (LTR) and after BCG vaccination in a short-term prospective analysis (STP). Four covariates were analysed: gender, country, BCG vaccination history and monocyte/lymphocyte cell count ratio. Univariable and multivariable linear regression were conducted on IFN-γ response at baseline for LTR, and area under the curve (AUC), 24 week and peak IFN-γ response for STP. Previous BCG vaccination was strongly associated with higher IFN-γ response at baseline (LTR analysis) (p-values response (p-value = 0.1). BCG revaccination was strongly associated with a larger response increase than primary-vaccination (AUC & peak p-values 0.1). This analysis suggests that previous BCG vaccination and gender are associated with durable IFN-γ responses. Vaccine trials may need to stratify by BCG vaccination history and gender. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Polymerase chain reaction based method for the detection of BCG retention after intravesical instillation in guinea pig bladders

    NARCIS (Netherlands)

    de Boer, E. C.; Westerhof, A. C.; Kolk, A. H.; Kuijper, S.; Kurth, K. H.; Schamhart, D. H.

    2000-01-01

    In intravesical Bacille bilié de Calmette-Guérin (BCG) immunotherapy of superficial bladder cancer, a T cell mediated immunological reaction is associated with the antitumor activity. To gain insight into the approximate number of BCG bacteria retained in the normal, noninjured, urinary bladder

  1. Immunotherapeutic effect of BCG-polysaccharide nucleic acid powder on Mycobacterium tuberculosis-infected mice using microneedle patches.

    Science.gov (United States)

    Yan, Qinying; Liu, Houming; Cheng, Zhigang; Xue, Yun; Cheng, Zhide; Dai, Xuyong; Shan, Wanshui; Chen, Fan

    2017-11-01

    Polysaccharide nucleic acid fractions of bacillus Calmette-Guérin, termed BCG-PSN, have traditionally been used as immunomodulators in the treatment of dermatitis and allergic diseases. While the sales of injectable BCG-PSN have shown steady growth in recent years, no reports of using BCG-PSN powder or its immunotherapeutic effects exist. Here, BCG-PSN powder was applied directly to the skin to evaluate the immunotherapeutic effects on mice infected with Mycobacterium tuberculosis (MTB). In total, 34 μg of BCG-PSN powder could be loaded into a microneedle patch (MNP). Mice receiving BCG-PSN powder delivered via MNP exhibited significantly increased IFN-γ and TNF-α production in peripheral blood CD4 + T cells and improved pathological changes in their lungs and spleens compared to control group mice. The immunotherapeutic effect of BCG-PSN powder delivered via MNP was better than that delivered via intramuscular injection to some extent. Furthermore, MNPs eliminate the side effects of syringes, and this study demonstrated that BCG-PSN can be clinically administrated in powder form.

  2. [The effect of PPS on location of rBCG in bladder cancer cell line T24].

    Science.gov (United States)

    Zeng, Xing; Yang, Ming; Wang, Jia; Zhang, Xian; Sun, Jing-Bo; Duan, Xiao-Jun

    2007-11-01

    To investigate the effect of polyporus polysaccharide (PPS) on location of green fluorescent recombinant protein BCG in human bladder cancer cell line T24. A green fluorescent protein expressed with rBCG was used as reporter gene, and laser scanning confocal microscopy and flow cytometry(FCM) analysis were performed to examine the alteration of T24 cells stimulated with rBCG or rBCG plus PPS. Green fluorescence (86.335+/-5.856) was observed obviously in the cytoplasm of T24 cells after interaction with rBCG for 24 h. By FCM we found scatter dot signal in SS and FS channel from rBCG groups was stronger that a control at 24 h and 48 h respectively. Meanwhile the population of T24 cells deflected to upper right and the percentage of GFP(+) T24 cells detected in FL1 channel was (8.7+/-1.572)%, (13.8+/-2.31)% (PPPS groups, the fluorescence intensity increased in the nucleus (72.603+/-1.165), while decreased in the cytoplasm (93.06+/-0.958), thus the nucleus/plasm ratio increased (0.78+/-0.005). Compared to rBCG group (62.832+/-2.909, 105.306+/-6.393, 0.597+/-0.012), the difference was statistically significant (P<0.05). rBCG is able to enter directly into the cytoplasm of T24 cells.

  3. Recombinant BCG Expressing ESX-1 of Mycobacterium marinum Combines Low Virulence with Cytosolic Immune Signaling and Improved TB Protection.

    Science.gov (United States)

    Gröschel, Matthias I; Sayes, Fadel; Shin, Sung Jae; Frigui, Wafa; Pawlik, Alexandre; Orgeur, Mickael; Canetti, Robin; Honoré, Nadine; Simeone, Roxane; van der Werf, Tjip S; Bitter, Wilbert; Cho, Sang-Nae; Majlessi, Laleh; Brosch, Roland

    2017-03-14

    Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling. Here, by heterologously expressing the esx-1 region of Mycobacterium marinum in BCG, we engineered a low-virulence, ESX-1-proficient, recombinant BCG (BCG::ESX-1 Mmar ) that induces the cGas/STING/TBK1/IRF-3/type I interferon axis and enhances AIM2 and NLRP3 inflammasome activity, resulting in both higher proportions of CD8 + T cell effectors against mycobacterial antigens shared with BCG and polyfunctional CD4 + Th1 cells specific to ESX-1 antigens. Importantly, independent mouse vaccination models show that BCG::ESX-1 Mmar confers superior protection relative to parental BCG against challenges with highly virulent M. tuberculosis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months.

    Science.gov (United States)

    Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo; Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjaergaard, Jesper; Jensen, Aksel Karl Georg; Aaby, Peter; Olesen, Annette Wind; Stensballe, Lone Graff; Jeppesen, Dorthe Lisbeth; Benn, Christine Stabell; Kofoed, Poul-Erik

    2017-09-01

    Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age BCG group and 6.1% (126/2061) of the control group suspected food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0.91 (95% CI 0.71-1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65-1.36]). In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  5. Long-term in vitro and in vivo effects of gamma-irradiated BCG on innate and adaptive immunity

    NARCIS (Netherlands)

    Arts, R.J.W.; Blok, B.A.; Aaby, P.; Joosten, L.A.B.; Jong, D.J. de; Meer, J.W.M. van der; Benn, C.S.; Crevel, R. van; Netea, M.G.

    2015-01-01

    BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity but not in

  6. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

    NARCIS (Netherlands)

    Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris; Li, Yang; Wang, Shuang-Yin; Oosting, Marije; Kumar, Vinod; Xavier, Ramnik J; Wijmenga, Cisca; Joosten, Leo A B; Reusken, Chantal B E M; Benn, Christine S; Aaby, Peter; Koopmans, Marion P; Stunnenberg, Hendrik G; van Crevel, Reinout; Netea, Mihai G

    2018-01-01

    The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide

  7. Bacille Calmette-Guerin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    NARCIS (Netherlands)

    Nissen, T.N.; Birk, N.M.; Smits, G.; Jeppesen, D.L.; Stensballe, L.G.; Netea, M.G.; Klis, F. van der; Benn, C.S.; Pryds, O.

    2017-01-01

    INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guerin (BCG)

  8. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    NARCIS (Netherlands)

    Biering-Sorensen, S.; Jensen, K.J.; Aamand, S.H.; Blok, B.; Andersen, A.; Monteiro, I.; Netea, M.G.; Aaby, P.; Benn, C.S.; Haslov, K.R.

    2015-01-01

    INTRODUCTION: Bacille Calmette-Guerin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual

  9. Effects of Bacillus Calmette-Guerin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial

    NARCIS (Netherlands)

    Birk, N.M.; Nissen, T.N.; Kjaergaard, J.; Hartling, H.J.; Thostesen, L.M.; Kofoed, P.E.; Stensballe, L.G.; Andersen, A.; Pryds, O.; Netea, M.G.; Benn, C.S.; Nielsen, S.D.; Jeppesen, D.L.

    2017-01-01

    The Bacillus Calmette-Guerin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets,

  10. rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector

    NARCIS (Netherlands)

    Magalhaes, Isabelle; Sizemore, Donata R.; Ahmed, Raija K.; Mueller, Stefanie; Wehlin, Lena; Scanga, Charles; Weichold, Frank; Schirru, Giulia; Pau, Maria Grazia; Goudsmit, Jaap; Kühlmann-Berenzon, Sharon; Spångberg, Mats; Andersson, Jan; Gaines, Hans; Thorstensson, Rigmor; Skeiky, Yasir A. W.; Sadoff, Jerry; Maeurer, Markus

    2008-01-01

    BACKGROUND: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing

  11. BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301)

    International Nuclear Information System (INIS)

    Hayne, Dickon; Stockler, Martin; McCombie, Steve P.; Chalasani, Venu; Long, Anne; Martin, Andrew; Sengupta, Shomik; Davis, Ian D.

    2015-01-01

    Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use

  12. Dactilitis and oligoarthritis after BCG immunotherapy in a patient affected by bladder cancer

    Directory of Open Access Journals (Sweden)

    N. Elkhaldi

    2011-09-01

    Full Text Available The treatment of bladder cancer with Bacillus of Calmette-Guerin (BCG immunotherapy can induce the appearance of a reactive disorder. The Authors describe a 55-year-old male patient with bladder cancer treated with endovesical instillation of BCG immunotherapy, followed after the fifth application by asymmetric oligoarthritis and dactilitis. The observed positivity of both HLA-B27 and HLA-B51 antigens reinforces the hypothesis of a reactive form, possibly through "molecular mimicry" mechanism. The discontinuation of BCG instillation along which a therapeutic attempt with NSAD failed to improve the rheumatic manifestation, which completely remitted after a four-month course of oral steroids. No relapses of joint and tendon involvement was observed during the following five-month period. The clinico- pathogenetic implications suggested by this case are discussed.

  13. Lupus vulgaris at the site of BCG vaccination: report of three cases.

    Science.gov (United States)

    Farsinejad, K; Daneshpazhooh, M; Sairafi, H; Barzegar, M; Mortazavizadeh, M

    2009-07-01

    Lupus vulgaris (LV) is a rare complication of the bacille Calmette-Guérin (BCG) vaccination, and about 65 cases of inoculation tuberculosis resembling LV have been reported in the literature. We report three cases of LV, developing many years later at the inoculation site of BCG vaccine. All three cases had a single BCG vaccination, with a LV lesion at or in the vicinity of the vaccination site, a strong positive Mantoux test, noncaseating granuloma histologically, and two of the patients had a positive PCR result for mycobacterial complex. One of the patients had an unusually delayed appearance of the LV lesion, after an interval of about 17 years, and another case was remarkable because of the large size of the lesion (210 x 110 mm).

  14. Rapid protective effects of early BCG on neonatal mortality among low birth weight boys

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Monterio, Ivan

    2018-01-01

    .85 (0.46-1.54)), but a significant reduction in weeks 2-4 (MRR=0.56 (0.31-1.00)). This pattern was consistent in all three trials. The verbal autopsies linked the early benefit to fewer sepsis-related deaths among BCG-vaccinated boys. Discussion: The marked reduction in mortality in the first few days......Background: Three randomised trials (RCTs) in low-weight (LW, vaccine non-specifically reduces all-cause mortality in the neonatal period. Methods: Using data from three RCTs of early BCG (N=6,583) we examined potential sex......-differences in the timing of the mortality reduction in the neonatal period, presenting meta-estimates of the main outcome mortality rate ratios (MRR) for BCG-vaccinated and controls. Results: Among controls, boys had a particularly high mortality during the first week after randomisation, the male-female MRR being 2...

  15. How do parents make their decision about letting their child get a BCG vaccination?

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane

    focus for this project is parents decision making and risk evaluation. I want to investigate how parents make their decision about letting their child get a BCG vaccination and how they evaluate the risk of side effects. Method: Before the clinical trial was started, we conducted 5 focus groups......-analysis of the results shows, that some danish parents are still concerned about nondescribed and non-specific side effects, even if the BCG-vaccine has been used for over 100 years and the side effects is well-described in medical research. They express doubt about the medical descriptions of the side effects and wants...... to discuss it with a professional they trust before they can decide to let their child vaccinate with BCG or not. I will show how parents try to make their own risk evaluation on the basis of a lay epidemiology, as described by Davison, Frankel and Davey Smith (1). They use their own interpretation of cases...

  16. Haematological profile of rats (Rattus norvegicus) induced BCG and provided leaf extract of Plectranthus amboinicus Lour Spreng)

    Science.gov (United States)

    Silitonga, Melva; Silitonga, Pasar M.

    2017-08-01

    Plectranthus amboinicus Lour Spreng is a medicinal plant that has many benefits, such as an antioxidant, hepatoprotective and immunostimulan. Immune status can be seen from hematological profile. This study aims to investigate hematology profile on rats induced BCG and leaf extract of Plectranthus amboinicus. 24 male rats aged 3 months and weighing between 140-200 grams divided equally into six groups, P0, P1, P2, P3, P4 and P5. P0 as controle was given aquadest. The P1, P2, P3, P4 and P5 treatment groups were given 19 g / kg AEP + BCG, 31.5 g / kg AEP + BCG, 19g / kg AEP, 31.5 g / kg AEP and BCG consecutively. The BCG were used as antigen. The AEP was administered orally for 30 days and 100 µl BCG were intramusculary administered on day 14 th and day 21. On day 31st, the rats we decapitated and their blood were collected for hematology (leucocyte (WBC), Erythrocyte (RBC), thrombocyte (PLT) count, Haemoglobin (Hb), erythrocyte sedimentation rate (ESR), MCV, MHC, and MHCH analysis. Data were analyzed with ANOVA. WBC increased significantly in treatment AEP 31.5 g / kg bw, 31.5 g AEP / kg bw + BCG and so were only given BCG. RBC tend to increase in all AEP treatment but tends to increase again when given a BCG. Hb increased in treatment P1, P2, T3 and P4, but the improvement was significant only in treatment P1. While PLT increase significantly in all treatments compared to the controls. HCT did not show significant differences but all of them were in the normal range. EAP without BCG and with the addition of BCG lowered ESR significantly, whereas BCG alone increased the ESR significantly. MCV increased significantly only in the treatment of P1 and show the same pattern with the MHC and MHCH. The conclusion that Plectranthus amboinicus Lour a positive impact on blood profiles with and without BCG. Plectranthus amboinicus Lour managed blood profile when administered together with BCG

  17. Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie

    2015-01-01

    -Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4...... or -7/8, or purified protein derivative (PPD). RESULTS:  Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation......, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. CONCLUSION:  Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro...

  18. Extraction and localization by electron microscopy of an immunosuppressor fraction from Mycobacterium bovis Bacillus Calmette-Guérin (BCG).

    Science.gov (United States)

    Hiu, I J

    1990-03-01

    BCG has been used all over the world to immunize against tuberculosis. Nevertheless in certain areas (South India) BCG vaccines failed to show any protective efficacy. Furthermore immunosuppressive cell populations have been reported in experimental mycobacterial infection in mice. The present work reports the localization and isolation of an immunosuppressor fraction from BCG. This lipid fraction called WDB inhibited the skin reactivity of delayed-type hypersensitivity (DTH) to the test antigen CEWA (crystalline egg white albumin) in guinea pigs and depressed the production of immune antibody to SRBC (sheep red blood cells) in mice. WDB is a glycolipid with an approximate mol.wt. of 62,000. By electron microscopy, WDB was located among the BCG extracellular metabolic products (ECMP) surrounding the BCG cell wall.

  19. Towards precise tracking of electric-mechanical cardiac time intervals through joint ECG and BCG sensing and signal processing.

    Science.gov (United States)

    Haihong Zhang; Zimin Wang; Kejun Dong; Soon Huat Ng; Zhiping Lin

    2017-07-01

    Automatic tracking of intra-beat cardiac activities in ballistocardiogram (BCG) is a highly interesting yet technically challenging topic for cardiac monitoring, due to the signal's high susceptibility to various forms of distortions. In this paper, we aim to further investigate the BCG waveform detection from a signal processing and analysis viewpoint. We collect synchronized electrocardiography(ECG) and BCG recordings from four healthy human subjects using an in-house built multi-physiological monitoring device. Particularly, we study post-exercise ECG-BCG signals that embed considerable variation in the heart beat during the post-exercise recovery phase. Furthermore, we develop an efficient and interactive tool for detecting and marking ECG-BCG waveforms in each heart beat. Through analyzing the detected time interval signals, we explore new interesting patterns of dynamic associations between different time interval signals. At the same time, we call for development of improved detection algorithms to address robustness and accuracy issues.

  20. Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Zeuthen, J

    1991-01-01

    The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients...... during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained...... unchanged and so did the lectin induced production of IL-2. The results suggest that the effects of intravesical BCG on the immune system should be studied in lymphocytes isolated from the bladder....

  1. Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Wojciech Krajewski

    2014-03-01

    Full Text Available Bladder cancer (BCA is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines – IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  2. Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Sara S Dhanawade

    2015-01-01

    Full Text Available Background: There is considerable variation in BCG scar failure rate on available data and correlation between BCG scar and tuberculin conversion remains controversial. Through this study we aimed to determine the scar failure rate and tuberculin conversion in term infants vaccinated with BCG within the first month. Materials and Methods: A prospective cohort study was conducted among 85 consecutive infants weighing >2 kg attending the immunization clinic of a medical college hospital. Fifteen subjects who could not complete the follow up were excluded. Total of 70 cases were analyzed. All babies were administered 0.1 ml of BCG and examined at 3 months (+1 week for scar. Tuberculin test was done with 5TU PPD. An induration of >5 mm was considered positive. Statistical analysis was done using Microsoft Excel and SPSS-22. Results: Out of the 70 infants, 41 (58.6% were males. Although majority (72.9% of infants were vaccinated within 7 days, only 18 (25.7% received BCG within 48 hours of birth. Sixty-four (91.4% had a visible scar at 12 weeks post vaccination representing a scar failure rate of 8.6%. Tuberculin test was positive in 50 (71.4%. The mean ± s.d. for scar and tuberculin skin test (TST reaction size was 4.93 ± 2.01 mm and 6.01 ± 3.22 mm, respectively. The association between scar formation and tuberculin positivity was highly significant (P < 0.001. There was significant correlation between scar size and TST size (r = 0.401, P = 0.001 Conclusions: Less than 10% of infants fail to develop a scar following BCG vaccination. There is good correlation between scar positivity and tuberculin conversion.

  3. Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Nankabirwa, Victoria; Tumwine, James K; Namugga, Olive; Tylleskär, Thorkild; Ndeezi, Grace; Robberstad, Bjarne; Netea, Mihai G; Sommerfelt, Halvor

    2017-03-31

    Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants. This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1β, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda. A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants. ClinicalTrials.gov, identifier: NCT02606526 . Registered on 12 November 2015.

  4. A Complication of BCG Vaccine: A Case of Localized Cutaneous Abscess due to Mycobacterium bovis

    Directory of Open Access Journals (Sweden)

    Nathalie Lussier

    1999-01-01

    Full Text Available The attenuated bacille Calmette-Guérin (BCG vaccine is administered to prevent tuberculosis. Complications of vaccination are uncommon. A case of cutaneous abscess due to BCG is presented in a 24-year-old woman. The abscess developed at the inoculation site four weeks after vaccination. Routine Gram stain and bacterial cultures of the pus were negative. The auramine stain was positive. Mycobacterial cultures were positive after 14 and 18 days, using the BACTEC 12B bottle and Löwenstein-Jensen media, respectively. The mycobacteria were identified as Mycobacterium bovis, vaccinal strain by high-performance liquid chromatography and DNA probe assays.

  5. Intravesical BCG immunotherapy: Sepsis and multiorgan failure developed after traumatic catheterization

    Directory of Open Access Journals (Sweden)

    Tufan Cicek

    2014-02-01

    Full Text Available Intravesical Bacillus Calmette-Guerin (BCG instillation is a prophylactic therapy using for treating bladder cancer to prevent tumour progression and recurrence. Both local and systemic complications can arise after the installation. Although local complications are common , this therapy is generally well tolerated. Systemic complications are rarely than local complications but can be fatal. We report a case who died from severe complications such as sepsis, pneumonia, renal failure and granulomatous hepatitis after receiving the first maintanence installation of intravesical BCG immunotherapy for bladder transitional cell carcinoma.

  6. Extracellular forms of Mycobacterium bovis BCG in the mucosal lymphatic tissues following oral vaccination

    Directory of Open Access Journals (Sweden)

    Wenzel Czepluch

    2013-01-01

    Full Text Available Oral vaccination with BCG provides protective systemic immunity against pathogenic mycobacterial challenge. In this study, the anatomical distribution of Mycobacterium bovis BCG following oral vaccination was investigated. Replicating bacteria in the Peyer's patches and mesenteric lymph nodes were present as solitary rods or clusters of two to three bacteria, the majority of which were isolated ex vivo as extracellular forms. Only a minority were shown to be associated with typical antigen-presenting cells. Acid-fast staining of mast cell granules in lymphoid tissues revealed a potential pitfall for these analyses and may explain previous reports of acid-fast ‘coccoid’ forms of mycobacteria in tissues.

  7. Nonspecific effect of BCG vaccination at birth on early childhood infections

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Birk, Nina Marie; Nissen, Thomas N

    2016-01-01

    BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitm......BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during...... during the first 3 mo....

  8. Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

    2017-01-01

    are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. Objective: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. Methods: The Danish Calmette Study is a multicenter randomized trial conducted...... (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Conclusion: Neonatal BCG had no effect on the development of RW before 13 months of age....

  9. Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Wellington Bandeira da Silva

    2009-12-01

    grandes vacúolos. De forma geral, a inoculação de BCG em cascavéis desencadeia respostas inflamatórias hematológicas caracterizadas pela participação de trombócitos, granulócitos e azurófilos.The high demand for anti-venom production in response to the increased number of cases of snakebite envenomation highlights the importance of raising and breeding venomous snakes in captivity. Knowledge of types of venoms and anti-venoms is of great interest to public health. The maintenance of venomous serpents in captivity started in the early twentieth century, but still nowadays it is a challenge to manage and prevent diseases in captive fauna. Hematology is commonly used for general health assessment and illness detection. However, data on serpent blood analysis are still scarce. Alterations in hematological parameters were experimentally induced in rattlesnakes by the inoculation of BCG. Based on this, hemograms can be used as a health auxiliary diagnosis method for bacterial diseases in this species. In this study, blood samples were taken from 10 healthy specimens of rattlesnakes (Crotalus durissus born and bred in captivity in the Herpetological Division of Vital Brazil Institute. Animals were divided into two groups (group 1 and 2 with similar live weight and sex proportion, and were then inoculated subcutaneously with BCG (Bacillus Calmette-Guérin. Blood samples were taken before and after inoculation at three experimental times (days 3, 5 and 7 for group 1 and days 11, 17 and 21 for group 2. Hematological analysis was performed through semi-direct technique, blood samples were diluted in Natt and Herrick solution and smears were stained by Giemsa. Serpents from group 1 developed discrete anemia due to the inflammatory syndrome, and showed significant decrease of MCH and MCHC. Granulocytes were characterized by the presence of rough granules. The azurophils varied in shape and size and showed large amount of cytoplasmic vacuoles. The thrombocytopenia observed

  10. Commonly administered BCG strains including an evolutionarily early strain and evolutionarily late strains of disparate genealogy induce comparable protective immunity against tuberculosis.

    Science.gov (United States)

    Horwitz, Marcus A; Harth, Günter; Dillon, Barbara Jane; Maslesa-Galić, Sasa

    2009-01-14

    BCG has been administered to over 4 billion persons worldwide, but its efficacy in preventing tuberculosis in adults has been highly variable. One hypothesis for its variability is that different strains of BCG vary in protective efficacy, and moreover, that evolutionarily early strains are more efficacious than the more attenuated evolutionarily late strains, which lack region of deletion 2. To examine this hypothesis, we tested six widely used BCG strains--the evolutionarily early strain BCG Japanese, two evolutionarily late strains in DU2 Group III (BCG Danish and Glaxo), and three evolutionarily late strains in DU2 Group IV (BCG Connaught, Pasteur, and Tice)--in the guinea pig model of pulmonary tuberculosis. With the exception of BCG Glaxo, which had relatively poor efficacy, we found no substantial differences in efficacy between the early strain and the late strains, and only small differences in efficacy among late strains. BCG Tice was the most efficacious BCG vaccine, with significantly fewer Mycobacterium tuberculosis in the lung and spleen than BCG Danish and BCG Japanese, although absolute differences in the organ burden of M. tuberculosis among these three vaccines were small (Pasteur were not significantly different. rBCG30, a recombinant BCG Tice vaccine overexpressing the M. tuberculosis 30 kDa major secretory protein (Antigen 85B), was more potent than any BCG vaccine (P < 0.0001 for differences in organ burden). Our study shows that late strains are not less potent than an early strain and argues against strain differences as a major factor in the variability of outcomes in BCG vaccine trials.

  11. The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Prendergast, Kelly A; Counoupas, Claudio; Leotta, Lisa; Eto, Carolina; Bitter, Wilbert; Winter, Nathalie; Triccas, James A

    2016-05-17

    Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection. Ag85B was required for macrophage infection in vitro, as BCG deficient in Ag85B expression (BCG:(Δ85B)) was less able to infect RAW 264.7 macrophages compared to parental BCG, while an Ag85B-overexpressing BCG strain (BCG:(oex85B)) demonstrated improved uptake. A similar pattern was observed in vivo after intradermal delivery to mice, with significantly less BCG:(Δ85B) present in CD64(hi)CD11b(hi) macrophages compared to BCG or BCG:(oex85B). After vaccination of mice with BCG:(Δ85B) or parental BCG and subsequent aerosol M. tuberculosis challenge, similar numbers of activated CD4(+) and CD8(+) T cells were detected in the lungs of infected mice for both groups, suggesting the reduced macrophage uptake observed by BCG:(Δ85B) did not alter host immunity. Further, vaccination with both BCG:(Δ85B) and parental BCG resulted in a comparable reduction in pulmonary M. tuberculosis load. These data reveal an unappreciated role for Ag85B in the interaction of mycobacteria with host cells and indicates that single protective antigens are dispensable for protective immunity induced by BCG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Waste Package Lifting Calculation

    International Nuclear Information System (INIS)

    H. Marr

    2000-01-01

    The objective of this calculation is to evaluate the structural response of the waste package during the horizontal and vertical lifting operations in order to support the waste package lifting feature design. The scope of this calculation includes the evaluation of the 21 PWR UCF (pressurized water reactor uncanistered fuel) waste package, naval waste package, 5 DHLW/DOE SNF (defense high-level waste/Department of Energy spent nuclear fuel)--short waste package, and 44 BWR (boiling water reactor) UCF waste package. Procedure AP-3.12Q, Revision 0, ICN 0, calculations, is used to develop and document this calculation

  13. Packaging for Food Service

    Science.gov (United States)

    Stilwell, E. J.

    1985-01-01

    Most of the key areas of concern in packaging the three principle food forms for the space station were covered. It can be generally concluded that there are no significant voids in packaging materials availability or in current packaging technology. However, it must also be concluded that the process by which packaging decisions are made for the space station feeding program will be very synergistic. Packaging selection will depend heavily on the preparation mechanics, the preferred presentation and the achievable disposal systems. It will be important that packaging be considered as an integral part of each decision as these systems are developed.

  14. Anti-tumour research of recombinant BCG using BZLF1 and hGM-CSF fusion genes.

    Science.gov (United States)

    Xue, Qing-Jie; Li, Yun-Qing; Yang, Chun-Qing; Chen, Ting; Li, Xiu-Zhen; Cheng, Baohua; Wang, Chun-Mei

    2017-03-14

    The random primer Oligo(dT) 15 was used in RT-PCR to obtain cDNA from the human granulocyte macrophage colony stimulating factor (hGM-CSF) gene and the Epstein-Barr virus (EBV) gene BZLF1. Then, the sequence splicing overlap extension method was used to obtain a GCBF fusion gene containing a linker sequence that encoded the polypeptide (Gly 4 Ser) 3 . The GCBF fusion gene was inserted into pMV261, which was then transformed into competent E. coli DH5 alpha cells, and positive cells were selected based on kanamycin resistance on LB plates. The recombinant plasmid pMVBZLF1 was extracted from E. coli, and BCG (Bacillus Calmette-Guérin) was transformed into competent cells. According to the RT-PCR results, the target genes hGM-CSF and BZLF1 were 461bp and 788bp in size, which was in agreement with the expected values. Construction of the recombinant plasmid by double enzyme digestion, amplification, sequencing and Western blotting confirmed that the GCBF fusion gene (1204bp) was correctly inserted into pMV261, successfully transformed into BCG competent cells, and properly expressed. After mice were injected with rBCG (recombinant BCG), antibody levels were detected using ELISA, and spleen cells were obtained and the killing rates of specific CTLs by rBCG were detected using a CTL assay kit. Then, the influence of rBCG on tumour cells was analysed in C57BL/6 mice. We found that rBCG-secreting cytokines hybridized with hGM-CSF and BZLF1 antibodies and that the rBCG vaccine stimulated antibody production in C57BL/6 mice. The specific cytotoxic effects of the spleen cells from the rBCG group on EB virus-positive tumour cells was significantly different from the cytotoxic effects of the control group cells (P<0.01). CD8 + T and CD4 + T lymphocytes were detected in the tumour tissues of the rBCG group mice by flow cytometry, indicating that CD8 + T and CD4 + T lymphocytes infiltrated into the tumour tissue in the mice. Morphological observations of the tumour sections from

  15. A lipidated peptide of Mycobacterium tuberculosis resuscitates the protective efficacy of BCG vaccine by evoking memory T cell immunity.

    Science.gov (United States)

    Rai, Pradeep K; Chodisetti, Sathi Babu; Zeng, Weiguang; Nadeem, Sajid; Maurya, Sudeep K; Pahari, Susanta; Janmeja, Ashok K; Jackson, David C; Agrewala, Javed N

    2017-10-06

    The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice. Female BALB/c mice were immunized with BCG. Later, they were boosted twice with L91 or an antigenically irrelevant lipidated influenza virus hemagglutinin peptide (LH). Further, PBMCs obtained from BCG vaccinated healthy subjects were cultured in vitro with L91. T cell responses were determined by surface markers and intracellular cytokine staining. Secretion of cytokines was estimated in the culture supernatants (SNs) by ELISA. Compared to the BCG-vaccinated controls, L91 booster significantly enhanced the percentage of memory Th1 cells and Th17 cells and reduced the mycobacterial burden in BCG primed and L91-boosted (BCG-L91) group, even after 229 days of BCG vaccination. Further, substantial augmentation in the central (CD44 hi CD62L hi CD127 hi ) and effector memory (CD44 hi CD62L lo CD127 lo ) CD4 T cells was detected. Furthermore, greater frequency of polyfunctional Th1 cells (IFN-γ + TNF-α + ) and Th17 cells (IFN-γ + IL-17A + ) was observed. Importantly, BCG-L91 successfully prevented CD4 T cells from exhaustion by decreasing the expression of PD-1 and Tim-3. Additionally, augmentation in the frequency of Th1 cells, Th17 cells and memory CD4 T cells was observed in the PBMCs of the BCG-vaccinated healthy individuals following in vitro stimulation with L91. Our study demonstrated that L91 robustly reinvigorate BCG potency to invoke enduring protection against

  16. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-05-13

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

  17. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M.; Lucas, Megan; Spencer, John S.; Amara, Rama Rao; Plikaytis, Bonnie B.; Posey, James E.; Sable, Suraj B.

    2016-01-01

    Heterologous prime–boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32–52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime–Apa-subunit-boost strategy compared to Apa-subunit-prime–BCG-boost approach. However, parenteral BCG-prime–Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime–boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime–boost regimens against tuberculosis in humans. PMID:27173443

  18. Identification of surrogates and correlates of protection in protective immunity against Mycobacterium bovis infection induced in neonatal calves by vaccination with M. bovis BCG Pasteur and M. bovis BCG Danish.

    Science.gov (United States)

    Hope, J C; Thom, M L; McAulay, M; Mead, E; Vordermeier, H M; Clifford, D; Hewinson, R G; Villarreal-Ramos, B

    2011-03-01

    Vaccination of neonatal calves with Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces a significant degree of protection against infection with virulent M. bovis, the causative agent of bovine tuberculosis (bTB). We compared two strains of BCG, Pasteur and Danish, in order to confirm that the current European human vaccine strain (BCG Danish) induced protective immunity in calves, and we assessed immune responses to determine correlates of protection that could assist future vaccine evaluation in cattle. Both vaccine strains induced antigen (purified protein derivate [PPD])-specific gamma interferon (IFN-γ) in whole-blood cultures. These responses were not significantly different for BCG Pasteur and BCG Danish and peaked at week 2 to 4 postvaccination. Vaccination with either BCG Danish or BCG Pasteur induced significant protection against bTB, with reductions in both lesion score and bacteriological burden evident in both groups of vaccinated calves compared with nonvaccinated control calves. Measurement of IFN-γ-expressing T lymphocytes postvaccination and postchallenge revealed both correlates and surrogates of protective efficacy. The frequency of central memory T lymphocytes present at 12 weeks postvaccination (at the time of M. bovis challenge) correlated significantly with protection. Conversely, the number of IFN-γ-expressing effector T cells present after M. bovis challenge was correlated with disease. These results demonstrate that vaccination of neonatal calves with either BCG Pasteur or BCG Danish induces protective immune responses against TB. In addition, we show that measurement of antigen-specific T lymphocyte populations may provide a reliable means for identifying protective vaccine candidates.

  19. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn

    2015-01-01

    INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual de...... in the production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482).......INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual...

  20. Merganser Download Package

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data download package contains an Esri 10.0 MXD, file geodatabase and copy of this FGDC metadata record. The data in this package are used in support of the...

  1. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi...

  2. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2008-02-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α. For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the

  3. Packaging Printing Today

    OpenAIRE

    Stanislav Bolanča; Igor Majnarić; Kristijan Golubović

    2015-01-01

    Printing packaging covers today about 50% of all the printing products. Among the printing products there are printing on labels, printing on flexible packaging, printing on folding boxes, printing on the boxes of corrugated board, printing on glass packaging, synthetic and metal ones. The mentioned packaging are printed in flexo printing technique, offset printing technique, intaglio halftone process, silk – screen printing, ink ball printing, digital printing and hybrid printing process. T...

  4. Genome packaging in viruses

    OpenAIRE

    Sun, Siyang; Rao, Venigalla B.; Rossmann, Michael G.

    2010-01-01

    Genome packaging is a fundamental process in a viral life cycle. Many viruses assemble preformed capsids into which the genomic material is subsequently packaged. These viruses use a packaging motor protein that is driven by the hydrolysis of ATP to condense the nucleic acids into a confined space. How these motor proteins package viral genomes had been poorly understood until recently, when a few X-ray crystal structures and cryo-electron microscopy structures became available. Here we discu...

  5. Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants.

    Science.gov (United States)

    Hesseling, Anneke C; Blakney, Anna K; Jones, Christine E; Esser, Monika M; de Beer, Corena; Kuhn, Louise; Cotton, Mark F; Jaspan, Heather B

    2016-07-12

    Bacille Calmette-Guérin (BCG) is routinely given at birth in tuberculosis-endemic settings due to its protective effect against disseminated tuberculosis in infants. BCG is however contraindicated in HIV-infected infants. We investigated whether delaying BCG vaccination to 14 weeks of age affected vaccine-induced antibody responses to Haemophilus influenzae type b (Hib)-conjugate, pertussis, tetanus and Hepatitis B (HBV) vaccines, in HIV-exposed uninfected (HEU) and -unexposed uninfected (HUU) infants. Infants were randomized to receive BCG at birth or at 14 weeks of age. Blood was taken at 14, 24, and 52 weeks of age and analyzed for Hib, pertussis, tetanus and HBV specific antibodies. BCG was given either at birth (106 infants, 51 HEU) or at 14 weeks of age (74 infants, 50 HEU). The timing of BCG vaccination did not influence the antibody response to any antigen studied. However, in a non-randomized comparison, HEU infants had higher Hib antibody concentrations at weeks 14 and 24 (p=0.001 and BCG vaccination, was associated with antibody concentrations to Hib, pertussis, HBV and tetanus primary immunization. DOH-27-1106-1520. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty

    2014-01-01

    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  7. Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik

    2005-01-01

    =2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD...... reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1......, low birth weight, place of residence, education and civil status of mother. We reason that vaccination technique and BCG strain are important for PPD reaction and scarring in response to BCG vaccination. Considering that these responses are associated with better infant survival, the importance...

  8. Coley's toxin and BCG vaccine in prevention and treatment of malignant melanoma in humans

    Czech Academy of Sciences Publication Activity Database

    Kučerová, Petra; Vlasáková, Jitka; Červinková, Monika

    2017-01-01

    Roč. 28, č. 3 (2017), s. 124-128 ISSN 0954-139X R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : BCG vaccine * Coley´s toxin * cytokines Subject RIV: EC - Immunology OBOR OECD: Immunology

  9. What have we learned after 30 years of BCG intravesical therapy for superficial bladder cancer?

    Directory of Open Access Journals (Sweden)

    Marcos Tobias-Machado

    2009-12-01

    Full Text Available Objectives: To discuss the role of bacillus Calmette-Guérin (BCG immunotherapy in the treatment of superficial bladder cancer after 30 years of clinical experience. Methods: Research on LILACS and PubMed databases, including 31 clinical studies with scientific relevance and importance in the decision-making process. Results: The BCG therapy with induction and maintenance therapy seems to be the best practice in tumors classified as high risk when compared to intravesical chemotherapy. In management of carcinoma in situ, BCG is undoubtedly the therapy of choice, presenting 84.4% of efficacy. As an adjuvant treatment to transurethral resection, there was a 31% reduction in recurrence confirmed in four out of five meta-analyses assessed. The reduction in progression, despite preliminary favorable evidence, still needs further studies to be confirmed. Conclusions: Intravesical BCG is an excellent therapeutic option in cases of carcinoma in situ and it is recommended as an adjuvant treatment in tumors with a high risk of recurrence and progression.

  10. Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

    NARCIS (Netherlands)

    Bevers, R. F. M.; Kurth, K.-H.; Schamhart, D. H. J.

    2004-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been

  11. Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

    2017-01-01

    -Denmark” (intervention group; n = 2083) or “control” (local policy for LW and no BCG-Denmark; n = 2089) at discharge from the maternity ward or at first contact with the health center. The infants were randomized (1:1) without blinding in blocks of 24. Data was analyzed in Cox hazards models providing mortality rate...... ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0...... by 38% (MRR, 0.62; 95% CI, .46–.83) within the neonatal period and 16% (0.84; .71–1.00) by age 12 months.ConclusionEarly administration of BCG-Denmark in LW infants is associated with major reductions in mortality rate. It is important that all LW infants receive early BCG in areas with high neonatal...

  12. The effect of BCG vaccine from protection of type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mehmet Karaci

    2012-03-01

    As a result, we concluded that if BCG is vaccine is applied at least twice and , the first dose is gives in the newborn period may exert a protective effect for the development of type I DM in children . [J Contemp Med 2012; 2(1.000: 1-8

  13. Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection Against Bovine Tuberculosis

    Science.gov (United States)

    Previous work in small animal laboratory models of tuberculosis have shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacille Calmette-Guerin (BCG) to prime and Modified Vaccinia Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad8...

  14. Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

    Science.gov (United States)

    Perdomo, Carolina; Zedler, Ulrike; Kühl, Anja A.; Lozza, Laura; Saikali, Philippe; Sander, Leif E.; Vogelzang, Alexis; Kupz, Andreas

    2016-01-01

    ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. PMID:27879332

  15. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.

    2010-01-01

    Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...

  16. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.

    2010-01-01

    Objective To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Design Randomised trial, with follow-up to age 5. Setting A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inha...

  17. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment

    DEFF Research Database (Denmark)

    Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M

    2010-01-01

    BACKGROUND: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...

  18. CD4 and CD8 counts of Bacillus Calmette Guerin (BCG) vaccinated ...

    African Journals Online (AJOL)

    This study examines the cellular immune factors responsible for combating infections by assessing CD4 and CD8 counts of neonates (pre and post BCG vaccination). A total of 373 blood samples were collected from neonates that visited the immunization clinics at Irrua Specialist Teaching Hospital (ISTH), Irrua and Federal ...

  19. Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

    2017-01-01

    are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. Objective: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. Methods: The Danish Calmette Study is a multicenter randomized trial conducted...

  20. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

    Directory of Open Access Journals (Sweden)

    Bryan E Hart

    2016-12-01

    Full Text Available Buruli ulcer (BU vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

  1. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

    Science.gov (United States)

    Hart, Bryan E; Lee, Sunhee

    2016-12-01

    Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

  2. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy

    Science.gov (United States)

    Hart, Bryan E.

    2016-01-01

    Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine. PMID:27941982

  3. Trends in Food Packaging.

    Science.gov (United States)

    Ott, Dana B.

    1988-01-01

    This article discusses developments in food packaging, processing, and preservation techniques in terms of packaging materials, technologies, consumer benefits, and current and potential food product applications. Covers implications due to consumer life-style changes, cost-effectiveness of packaging materials, and the ecological impact of…

  4. The Glycosylated Rv1860 Protein of Mycobacterium tuberculosis Inhibits Dendritic Cell Mediated TH1 and TH17 Polarization of T Cells and Abrogates Protective Immunity Conferred by BCG

    Science.gov (United States)

    Satchidanandam, Vijaya; Kumar, Naveen; Jumani, Rajiv S.; Challu, Vijay; Elangovan, Shobha; Khan, Naseem A.

    2014-01-01

    We previously reported interferon gamma secretion by human CD4+ and CD8+ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB) as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH17-dominated

  5. BCG-mediated protection against Mycobacterium ulcerans infection in the mouse.

    Directory of Open Access Journals (Sweden)

    Paul J Converse

    2011-03-01

    Full Text Available Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG is widely used to reduce the risk of childhood tuberculosis and has been reported to have efficacy against two other mycobacterial diseases, leprosy and Buruli ulcer caused by M. ulcerans (Mu. Studies in experimental models have also shown some efficacy against infection caused by Mu. In mice, most studies use the C57BL/6 strain that is known to develop good cell-mediated protective immunity. We hypothesized that there may be differences in vaccination efficacy between C57BL/6 and the less resistant BALB/c strain.We evaluated BCG vaccine efficacy against challenge with ∼3×10(5M. ulcerans in the right hind footpad using three strains: initially, the Australian type strain, designated Mu1617, then, a Malaysian strain, Mu1615, and a recent Ghanaian isolate, Mu1059. The latter two strains both produce mycolactone while the Australian strain has lost that capacity. CFU of both BCG and Mu and splenocyte cytokine production were determined at intervals after infection. Time to footpad swelling was assessed weekly.BCG injection induced visible scars in 95.5% of BALB/c mice but only 43.4% of C57BL/6 mice. BCG persisted at higher levels in spleens of BALB/c than C57BL/6 mice. Vaccination delayed swelling and reduced Mu CFU in BALB/c mice, regardless of challenge strain. However, vaccination was only protective against Mu1615 and Mu1617 in C57BL/6 mice. Possible correlates of the better protection of BALB/c mice included 1 the near universal development of BCG scars in these mice compared to less frequent and smaller scars observed in C57BL/6 mice and 2 the induction of sustained cytokine, e.g., IL17, production as detected in the spleens of BALB/c mice whereas cytokine production was significantly reduced, e.g., IL17, or transient, e.g., Ifnγ, in the spleens of C57BL/6 mice.The efficacy of BCG against M. ulcerans, in particular, and possibly mycobacteria in general, may vary due to

  6. Development of BCG Scar and Subsequent Morbidity and Mortality in Rural Guinea-Bissau.

    Science.gov (United States)

    Storgaard, Line; Rodrigues, Amabelia; Martins, Cesario; Nielsen, Bibi Uhre; Ravn, Henrik; Benn, Christine Stabell; Aaby, Peter; Fisker, Ane Bærent

    2015-09-15

    Previous studies have found that BCG vaccination has nonspecific beneficial effects on child survival, especially among children who developed a BCG scar. These studies have mostly been done in settings with a high scar frequency. In rural Guinea-Bissau, many children do not develop a scar; we tested the hypothesis that among BCG-vaccinated children, a vaccination scar was associated with lower mortality and fewer hospital admissions. During 2009-2011, children Health Project's demographic surveillance system had their scar status assessed at semiannual visits. We compared mortality and hospital admission rates of scar-positive and scar-negative BCG-vaccinated children during 6 months of follow-up in Cox proportional hazards models. Among 15 911 BCG-vaccinated children, only 52% had a scar. There were 106 non-injury-related deaths among scar-positive children and 137 among scar-negative children. The mortality rate ratio (MRR) was 0.74 (95% confidence interval [CI], .56-.96) overall; 0.48 (95% CI, .26-.90) in infancy, 0.69 (95% CI, .45-1.05) in the second year of life, and 0.89 (95% CI, .61-1.31) in the third-fifth year of life. The association between scar positivity and lower mortality differed significantly by cause of death and was strongest for respiratory infections (MRR, 0.20 [95% CI, .07-.55]). There were 99 hospital admissions among scar-positive children and 125 admissions among scar-negative children, resulting in an incidence rate ratio of 0.74 (95% CI, .60-.92). Among BCG-vaccinated children in a setting with low scar prevalence, having a scar is associated with lower mortality and morbidity. BCG scar prevalence may be an important marker of vaccination program quality. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Non-specific effects of BCG vaccination on morbidity among children in Greenland: a population-based cohort study.

    Science.gov (United States)

    Haahr, S; Michelsen, S W; Andersson, M; Bjorn-Mortensen, K; Soborg, B; Wohlfahrt, J; Melbye, M; Koch, A

    2016-12-01

    The potential non-specific effects of BCG (Bacillus Calmette-Guérin) vaccination, with reported reduction of infectious disease morbidity among vaccinated children, in addition to the protective effect against tuberculosis (TB), are highly debated. In Greenland, BCG vaccination was introduced in 1955, but temporarily discontinued from 1991 to 1996 due to nationwide policy changes. Using the transient vaccination stop, we aimed to investigate possible non-specific effects of BCG vaccination by measuring nation-wide hospitalization rates due to infectious diseases other than TB among vaccinated and unvaccinated children. A retrospective cohort study including all children born in Greenland aged 3 months to 3 years from 1989 to 2004. A personal identification number assigned at birth allowed for follow-up through national registers. Information on hospitalization due to infectious diseases was obtained from the Greenlandic inpatient register using ICD-8 and ICD-10 codes. Participants with notified TB were censored. Incidence rate ratios (IRR) were estimated using Poisson regression. Overall, 19 363 children, hereof 66% BCG-vaccinated, were followed for 44 065 person-years and had 2069 hospitalizations due to infectious diseases. IRRs of hospitalization in BCG-vaccinated as compared with BCG-unvaccinated children were 1.07 [95% confidence interval (CI) 0.96-1.20] for infectious diseases overall, and specifically 1.10 (95% CI 0.98-1.24) for respiratory tract infections. Among BCG-vaccinated children aged 3 to 11 months, the IRR of hospitalization due to infectious diseases was 1.00 (95% CI 0.84-1.19) as compared with BCG-unvaccinated children. Our results do not support the hypothesis that neonatal BCG vaccination reduces morbidity in children caused by infectious diseases other than TB. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  8. Could Hyaluronic acid (HA) reduce Bacillus Calmette-Guérin (BCG) local side effects? Results of a pilot study

    Science.gov (United States)

    2014-01-01

    Background Bacillus Calmette-Guérin (BCG) is considered the most effective treatment to reduce recurrence and progression of non-muscle invasive bladder cancer (NMIBC) but can induce local side effects leading to treatment discontinuation or interruption. Aim of this exploratory study is to investigate if the sequential administration of Hyaluronic acid (HA) may reduce local side effects of BCG. Methods 30 consecutive subjects undergoing BCG intravesical administration for high risk NMIBC were randomized to receive BCG only (Group A) or BCG and HA (Group B). A 1 to 10 Visual Analog Scale (VAS) for bladder pain, International Prostate Symptom Score (IPSS) and number of micturitions per day were evaluated in the two groups before and after six weekly BCG instillations. Patients were also evaluated at 3 and 6 months by means of cystostopy and urine cytology. Results One out of 30 (3,3%) patients in group A dropped out from the protocol, for local side effects. Mean VAS for pain was significantly lower in group B after BCG treatment (4.2 vs. 5.8, p = 0.04). Post vs. pre treatment differences in VAS for pain, IPSS and number of daily micturitions were all significantly lower in group B. Three patients in group A and 4 in group B presented with recurrent pathology at 6 month follow up. Conclusions These preliminary data suggest a possible role of HA in reducing BCG local side effects and could be used to design larger randomized controlled trials, assessing safety and efficacy of sequential BCG and HA administration. Trial registration NCT02207608 (ClinicalTrials.gov) 01/08/2014 Policlinico Tor Vergata Ethics Committee, resolution n 69–2011. PMID:25123116

  9. Human β-defensin 2 may inhibit internalisation of bacillus Calmette-Guérin (BCG) in bladder cancer cells.

    Science.gov (United States)

    Kim, Jung Hoon; Kim, Soon-Ja; Lee, Kyung Mee; Chang, In Ho

    2013-10-01

    To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells. Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments. BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells. © 2013 The Authors. BJU International © 2013 BJU International.

  10. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.

    Science.gov (United States)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby; Jeppesen, Dorthe Lisbeth; Stensballe, Lone Graff; Netea, Mihai G; van der Klis, Fiona; Benn, Christine Stabell; Pryds, Ole

    2017-04-11

    BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress.

    Directory of Open Access Journals (Sweden)

    James L Gallant

    Full Text Available We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH and glutamine oxoglutarate aminotransferase (GOGAT in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult.

  12. ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hu, E-mail: austhudong@126.com [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China); Jing, Wu, E-mail: wujing8008@126.com [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China); Runpeng, Zhao; Xuewei, Xu; Min, Mu; Ru, Cai [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Yingru, Xing; Shengfa, Ni [Affiliated Cancer Hospital, Anhui University of Science and Technology (China); Rongbo, Zhang [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China)

    2016-08-19

    In recent years, increasing studies have found that pathogenic Mycobacterium tuberculosis (Mtb) inhibits autophagy, which mediates the anti-mycobacterial response, but the mechanism is not clear. We previously reported that secretory acid phosphatase (SapM) of Mtb can negatively regulate autophagy flux. Recently, another virulence factor of Mtb, early secretory antigenic target 6 (ESAT6), has been found to be involved in inhibiting autophagy, but the mechanism remains unclear. In this study, we show that ESAT6 hampers autophagy flux to boost bacillus Calmette-Guerin (BCG) proliferation and reveals a mechanism by which ESAT6 blocks autophagosome-lysosome fusion in a mammalian target of rapamycin (MTOR)-dependent manner. In both Raw264.7 cells and primary macrophages derived from the murine abdominal cavity (ACM), ESAT6 repressed autophagy flux by interfering with the autophagosome-lysosome fusion, which resulted in an increased load of BCG. Impaired degradation of LC3Ⅱ and SQSTM1 by ESAT6 was related to the upregulated activity of MTOR. Contrarily, inhibiting MTOR with Torin1 removed the ESAT6-induced autophagy block and lysosome dysfunction. Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 blocks autophagy and promotes BCG survival in a way that activates MTOR. - Highlights: • A mechanism for disruping autophagy flux induced by ESAT6. • ESAT6-inhibited autophagy is MTOR-dependent. • ESAT6-boosted BCG is MTOR-dependent.

  13. Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy

    Directory of Open Access Journals (Sweden)

    Raffaella Rossi

    2013-12-01

    Full Text Available Objectives: Immunotherapy with BCG (Bacille Calmette-Guérin after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy Material and method: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. Results: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn’t find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn’t find mDCs in urine during monthly instillation. Conclusions: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation.

  14. Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress.

    Science.gov (United States)

    Gallant, James L; Viljoen, Albertus J; van Helden, Paul D; Wiid, Ian J F

    2016-01-01

    We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH) and glutamine oxoglutarate aminotransferase (GOGAT) in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult.

  15. Bacillus Calmette-Guérin (BCG) Vaccination in Infancy and Risk of Childhood Diabetes.

    Science.gov (United States)

    Rousseau, Marie-Claude; El-Zein, Mariam; Conus, Florence; Legault, Laurent; Parent, Marie-Elise

    2016-03-01

    A narrow time window in infancy may be relevant for the aetiology of immune-mediated type 1 diabetes. We investigated whether a non-specific immune stimulation in the first year of life, as resulting from Bacillus Calmette-Guérin (BCG) vaccination, was associated with childhood diabetes. Using data from a birth cohort assembled through linkage of administrative databases, 78,492 subjects born in 1974 were the object of the present analysis. Information was extracted from the birth, death, and BCG vaccination registries. Diabetes-related health services were obtained from administrative health databases (physician billing claims and hospitalisation data) until 1994. Subjects were classified as having diabetes according to two validated definitions: (1) ≥2 diabetes-related medical visits within 2 years or ≥1 hospitalisation for diabetes; and 2) ≥4 diabetes-related medical visits within 2 years. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI), adjusted for potential confounders. Forty-four per cent of subjects were BCG vaccinated in the first year of life. According to the first and second definition, respectively, 293 (0.37%) and 230 (0.29%) subjects were classified as having diabetes. There was no association between BCG vaccination in the first year of life and risk of diabetes with either definition (HR(def1)  = 0.92, 95% CI 0.73, 1.17; HR(def2)  = 1.04, 95% CI 0.80, 1.37), and results did not differ by sex. Given the potentially critical importance of the exposure window and paucity of studies addressing BCG vaccination timing in relation to diabetes risk, this question deserves further investigation. © 2015 John Wiley & Sons Ltd.

  16. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells

    Science.gov (United States)

    Hunsawong, Taweewun; Sunintaboon, Panya; Warit, Saradee; Thaisomboonsuk, Butsaya; Jarman, Richard G.; Yoon, In-Kyu; Ubol, Sukathida; Fernandez, Stefan

    2015-01-01

    Dengue viruses (DENVs) are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world’s population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV) composed of UV-inactivated DENV-2 (UVI-DENV) and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs) loaded into chitosan nanoparticles (CS-NPs). CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs) resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR) and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines. PMID:26394138

  17. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Taweewun Hunsawong

    2015-09-01

    Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

  18. The effect of the administration of human gamma globulins in a model of BCG infection in mice.

    Science.gov (United States)

    Olivares, Nesty; León, Annette; López, Yamilé; Puig, Alina; Cádiz, Armando; Falero, Gustavo; Martínez, Máximo; Sarmiento, Marie E; Fariñas, Mildrey; Infante, Juan F; Sierra, Gustavo; Solís, Rosa L; Acosta, Armando

    2006-01-01

    The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.

  19. Rapid Protective Effects of Early BCG on Neonatal Mortality Among Low Birth Weight Boys: Observations From Randomized Trials

    DEFF Research Database (Denmark)

    Biering-Sorensen, Sofie; Jensen, Kristoffer Jarlov; Monterio, Ivan

    2018-01-01

    Background. Three randomized trials (RCTs) in low-weight (....46–1.54]), but a significant reduction in weeks 2–4 (MRR = 0.56 [0.31–1.00]). This was consistent in all 3 trials. Verbal autopsies linked early benefit to fewer sepsis-related deaths among BCG-vaccinated boys. Discussion. The marked reduction in mortality in the days after BCG vaccination in boys emphasizes the importance...... of providing BCG soon after birth. Trial registration numbers: ClinicalTrials.gov (NCT00146302) and ClinicalTrials.gov (NCT00625482)....

  20. Advancements in meat packaging.

    Science.gov (United States)

    McMillin, Kenneth W

    2017-10-01

    Packaging of meat provides the same or similar benefits for raw chilled and processed meats as other types of food packaging. Although air-permeable packaging is most prevalent for raw chilled red meat, vacuum and modified atmosphere packaging offer longer shelf life. The major advancements in meat packaging have been in the widely used plastic polymers while biobased materials and their integration into composite packaging are receiving much attention for functionality and sustainability. At this time, active and intelligent packaging are not widely used for antioxidant, antimicrobial, and other functions to stabilize and enhance meat properties although many options are being developed and investigated. The advances being made in nanotechnology will be incorporated into food packaging and presumably into meat packaging when appropriate and useful. Intelligent packaging using sensors for transmission of desired information and prompting of subsequent changes in packaging materials, environments or the products to maintain safety and quality are still in developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Radiopharmaceuticals package monitoring system

    International Nuclear Information System (INIS)

    Farias, Marcos S.; Oliveira, Mauro V.; Aghina, Mauricio A.C.; Grecco, Claudio H.S.; Wendhausen, Marcos A.S.

    2011-01-01

    Radiopharmaceuticals are used in the field of nuclear medicine as tracers in the diagnosis and treatment of many diseases. The production of a radiopharmaceutical involves two main processes: the production of the radionuclide on which the pharmaceutical is based, and the preparation and packaging of the complete radiopharmaceutical. Before dispatching package radiopharmaceuticals to the users, each package must be labeling according to the maximum radiation level measured at its surface, according to the radiation protection guidelines CNEN-NE-5.01, to ensure that transport containers comply with regulatory requirements for transport of radiopharmaceuticals. This work describes the package monitoring system developed for help to radioprotection personnel in the process of monitor package radiopharmaceuticals. The system was installed and tested at IEN's dispatch package radiopharmaceuticals room and showed good contribution to reduce the radiation dose to the radioprotection personnel during the package measure process. (author)

  2. Edible packaging materials.

    Science.gov (United States)

    Janjarasskul, Theeranun; Krochta, John M

    2010-01-01

    Research groups and the food and pharmaceutical industries recognize edible packaging as a useful alternative or addition to conventional packaging to reduce waste and to create novel applications for improving product stability, quality, safety, variety, and convenience for consumers. Recent studies have explored the ability of biopolymer-based food packaging materials to carry and control-release active compounds. As diverse edible packaging materials derived from various by-products or waste from food industry are being developed, the dry thermoplastic process is advancing rapidly as a feasible commercial edible packaging manufacturing process. The employment of nanocomposite concepts to edible packaging materials promises to improve barrier and mechanical properties and facilitate effective incorporation of bioactive ingredients and other designed functions. In addition to the need for a more fundamental understanding to enable design to desired specifications, edible packaging has to overcome challenges such as regulatory requirements, consumer acceptance, and scaling-up research concepts to commercial applications.

  3. Plastic food packaging and health

    Directory of Open Access Journals (Sweden)

    Raika Durusoy

    2011-02-01

    Full Text Available Plastics have a wide usage in our daily lives. One of their uses is for food packaging and food containers. The aim of this review is to introduce different types of chemicals that can leach from food packaging plastics into foods and cause human exposure and to mention their effects on health. The types of plastics were reviewed under the 13 headings in Turkish Codex Alimentarius and plastics recycling symbols were provided to enable the recognition of the type of plastic when applicable. Chemicals used during the production and that can cause health risks are investigated under the heading of the relevant type of plastic. The most important chemicals from plastic food packaging that can cause toxicity are styrene, 1,3-butadiene, melamine, formaldehyde, acrylamide, di-2-ethylhexyl phthalate, di-2-ethylhexyl adipate, vinyl chloride and bisphenol A. These chemicals have endocrine disrupting, carcinogenic and/or development disrupting effects. These chemicals may leach into foods depending on the chemical properties of the plastic or food, temperature during packaging, processing and storage, exposure to UV and duration of storage. Contact with fatty/oily or acidic foods, heating of the food inside the container, or drinking hot drinks from plastic cups, use of old and scratched plastics and some detergents increase the risk of leaching. The use of plastic containers and packaging for food and beveradges should be avoided whenever possible and when necessary, less harmful types of plastic should be preferred. [TAF Prev Med Bull 2011; 10(1.000: 87-96

  4. Smac mimetic enables the anticancer action of BCG-stimulated neutrophils through TNF-α but not through TRAIL and FasL

    Science.gov (United States)

    Jinesh G., Goodwin; Chunduru, Srinivas; Kamat, Ashish M.

    2012-01-01

    BCG, the current gold standard immunotherapy for bladder cancer, exerts its activity via recruitment of neutrophils to the tumor microenvironment. Many patients do not respond to BCG therapy, indicating the need to understand the mechanism of action of BCG-stimulated neutrophils and to identify ways to overcome resistance to BCG therapy. Using isolated human neutrophils stimulated with BCG, we found that TNF-α is the key mediator secreted by BCG-stimulated neutrophils. RT4v6 human bladder cancer cells, which express TNFR1, CD95/Fas, CD95 ligand/FasL, DR4, and DR5, were resistant to BCG-stimulated neutrophil conditioned medium but effectively killed by the combination of conditioned medium and Smac mimetic. rhTNF-α and rhFasL, but not rhTRAIL, in combination with Smac mimetic, generated signature molecular events similar to those produced by BCG-stimulated neutrophils in combination with Smac mimetic. However, experiments using neutralizing antibodies to these death ligands showed that TNF-α secreted from BCG-stimulated neutrophils was the key mediator of anticancer action. These findings explain the mechanism of action of BCG and identified Smac mimetics as potential combination therapeutic agents for bladder cancer. PMID:22517918

  5. Lymph node targeting of BCG vaccines amplifies CD4 and CD8 T-cell responses and protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Waeckerle-Men, Ying; Bruffaerts, Nicolas; Liang, Yuan; Jurion, Fabienne; Sander, Peter; Kündig, Thomas M; Huygen, Kris; Johansen, Pål

    2013-02-04

    Vaccination with Mycobacterium bovis BCG provides limited protection against pulmonary tuberculosis and a risk of dissemination in immune-compromised vaccinees. For the development of new TB vaccines that stimulate strong T-cell responses a variety of strategies is being followed, especially recombinant BCG and attenuated M. tuberculosis. The objective of the current study was to test potential benefits of vaccination through direct lymph-node targeting of wildtype BCG; the recommended route of vaccination with BCG is intradermal. C57BL/6 mice were immunised with BCG by intradermal, subcutaneous or intralymphatic injections. Cellular immune responses and protection against M. tuberculosis were determined. Intralymphatic vaccination was 100-1000 times more effective in stimulating BCG-specific immune responses than intradermal or subcutaneous immunisation. Intralymphatic administration stimulated high frequencies of mycobacterium-specific lymphocytes with strong proliferating capacity and production of TNF-α, IL-2, IL-17 and, especially, IFN-γ secretion by. CD4 and CD8 T cells. Most importantly, intralymphatic vaccination with 2×10(3)CFU BCG induced sustained protection against M. tuberculosis in intratracheally challenged C57BL/6 mice, whereas subcutaneous vaccination with 2×10(5)CFU BCG conferred only a transient protection. Hence, direct administration of M. bovis BCG to lymph nodes demonstrates that efficient targeting to lymph nodes may help to overcome the efficacy problems of vaccination with BCG. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

    Science.gov (United States)

    Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

    2016-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

  7. Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis

    Science.gov (United States)

    Gengenbacher, Martin; Nieuwenhuizen, Natalie; Vogelzang, Alexis; Liu, Haipeng; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Wagner, Ina; Mollenkopf, Hans-Joachim

    2016-01-01

    ABSTRACT The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly. In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways. In mice, BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved protection over that of parental BCG ΔureC::hly, significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG ΔureC::hly or BCG ΔureC::hly ΔnuoG demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG ΔureC::hly ΔnuoG is a promising next-generation TB vaccine candidate with excellent efficacy and safety. PMID:27222470

  8. PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4+T cell transcriptomal molecular signatures.

    Science.gov (United States)

    Hoft, D F; Xia, M; Zhang, G L; Blazevic, A; Tennant, J; Kaplan, C; Matuschak, G; Dube, T J; Hill, H; Schlesinger, L S; Andersen, P L; Brusic, V

    2017-08-30

    Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4 + memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.Mucosal Immunology advance online publication 30 August 2017; doi:10.1038/mi.2017.67.

  9. Relative Efficacy of Uptake and Presentation of Mycobacterium bovis BCG Antigens by Type I Mouse Lung Epithelial Cells and Peritoneal Macrophages ▿

    Science.gov (United States)

    Kumari, Mandavi; Saxena, Rajiv K.

    2011-01-01

    Flow cytometric studies indicated that both peritoneal macrophages (PMs) and primary lung epithelial (PLE) cells isolated from mouse lungs could take up fluorescence-tagged Mycobacterium bovis BCG. BCG uptake in both cases was significantly inhibited by cytochalasin D, indicating active internalization of BCG by these cells. Confocal microscopy data further confirmed that BCG was internalized by PLE cells. BCG sonicate antigen (sBCG) had marked toxicity toward PMs but was relatively nontoxic to PLE cells. Accordingly, BCG sonicate antigen induced a significantly higher apoptotic and necrotic response in PMs compared to that in PLE cells. Both PMs and PLE cells exposed to BCG antigens and fixed thereafter could efficiently present antigens to purified BCG-sensitized T helper cells, as assessed by the release of interleukin-2 (IL-2) and gamma interferon (IFN-γ). If, however, PLE cells were fixed before exposure to BCG, antigen presentation was abrogated, indicating that the PLE cells may in some way process the BCG antigen. A comparison of efficacies of BCG-pulsed PLE cells and PMs to present antigen at various antigen-presenting cell (APC)/T cell ratios indicated that PMs had only marginally greater APC function than that of PLE cells. Staining with specific monoclonal antibodies indicated that the cultured PLE cells used for antigen presentation essentially comprised type I epithelial cells. Our results suggest that type I lung epithelial cells may present BCG antigens to sensitized T helper cells and that their performance as APCs is comparable with that of PMs. PMID:21646448

  10. A late presentation of isolated lymph node tuberculosis postintravesical BCG therapy for superficial bladder cancer: a novel case.

    Science.gov (United States)

    Tasleem, Ali Moostapha; Varga, Branislav; Mahmalji, Wasim; Madaan, Sanjeev

    2014-05-02

    Intravesical BCG immunotherapy is commonly used in the treatment of superficial bladder cancer. We recount the case of an 82-year-old British man who completed a course of BCG immunotherapy in 2011 for superficial bladder cancer, and presented in January 2013 with a loss of appetite, loss of weight and severe back pain. CT scanning, followed by MRI displayed a 5.7 cm × 5 cm conglomerated necrotic, haemorrhagic mass of lymph nodes in the para-aortic region. A CT-guided biopsy revealed granulomatous inflammation, focal fibrosis and acid-fast bacilli consistent with Mycobacterium tuberculosis (TB). The patient was treated with combination antituberculous medication, and is recovering. To our knowledge, this is the only reported case of lymph node TB secondary to intravesical BCG immunotherapy. We suggest that in patients treated with postintravesical BCG with enlarged lymph nodes, a diagnosis of secondary TB should be considered.

  11. Recombinant BCG Expressing ESX-1 of Mycobacterium marinum Combines Low Virulence with Cytosolic Immune Signaling and Improved TB Protection

    NARCIS (Netherlands)

    Gröschel, Matthias I.; Sayes, Fadel; Shin, Sung Jae; Frigui, Wafa; Pawlik, Alexandre; Orgeur, Mickael; Canetti, Robin; Honore, Nadine; Simeone, Roxane; van der Werf, Tjip S.; Bitter, Wilbert; Cho, Sang-Nae; Majlessi, Laleh; Brosch, Roland

    2017-01-01

    Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacteriumbovis BCG, provides limited

  12. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

    Science.gov (United States)

    Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

    2016-01-01

    Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

  13. Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo

    2017-01-01

    the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. METHODS: The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG...... sampling at 13 months of age. RESULTS: By 13 months of age, the parents and/or general practitioners of 5.6% (117/2089) of the children in the BCG group and 6.1% (126/2061) of the control group suspected food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0...... effect on suspected food allergy or on sensitization at 13 months of age....

  14. The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles).

    Science.gov (United States)

    Chambers, Mark A; Aldwell, Frank; Williams, Gareth A; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J; Nunez, Alejandro; Nadian, Allan K; Crawshaw, Timothy; Corner, Leigh A L; Lesellier, Sandrine

    2017-01-01

    The European badger ( Meles meles ) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 10 8 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB

  15. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  16. A diatom-based biological condition gradient (BCG) approach for assessing impairment and developing nutrient criteria for streams.

    Science.gov (United States)

    Hausmann, Sonja; Charles, Donald F; Gerritsen, Jeroen; Belton, Thomas J

    2016-08-15

    Over-enrichment leading to excess algal growth is a major problem in rivers and streams. Regulations to protect streams typically incorporate nutrient criteria, concentrations of phosphorus and nitrogen that should not be exceeded in order to protect biological communities. A major challenge has been to develop an approach for both categorizing streams based on their biological conditions and determining scientifically defensible nutrient criteria to protect the biotic integrity of streams in those categories. To address this challenge, we applied the Biological Condition Gradient (BCG) approach to stream diatom assemblages to develop a system for categorizing sites by level of impairment, and then examined the related nutrient concentrations to identify potential nutrient criteria. The six levels of the BCG represent a range of ecological conditions from natural (1) to highly disturbed (6). A group of diatom experts developed a set of rules and a model to assign sites to these levels based on their diatom assemblages. To identify potential numeric nutrient criteria, we explored the relation of assigned BCG levels to nutrient concentrations, other anthropogenic stressors, and possible confounding variables using data for stream sites in New Jersey (n=42) and in surrounding Mid-Atlantic states, USA (n=1443). In both data sets, BCG levels correlated most strongly with total phosphorus and the percentage of forest in the watershed, but were independent of pH. We applied Threshold Indicator Taxa Analysis (TITAN) to determine change-points in the diatom assemblages along the BCG gradient. In both data sets, statistically significant diatom changes occurred between BCG levels 3 and 4. Sites with BCG levels 1 to 3 were dominated by species that grow attached to surfaces, while sites with BCG scores of 4 and above were characterized by motile diatoms. The diatom change-point corresponded with a total phosphorus concentration of about 50μg/L. Copyright © 2016 Elsevier B

  17. Packaging for Sustainability

    CERN Document Server

    Lewis, Helen; Fitzpatrick, Leanne

    2012-01-01

    The packaging industry is under pressure from regulators, customers and other stakeholders to improve packaging’s sustainability by reducing its environmental and societal impacts. This is a considerable challenge because of the complex interactions between products and their packaging, and the many roles that packaging plays in the supply chain. Packaging for Sustainability is a concise and readable handbook for practitioners who are trying to implement sustainability strategies for packaging. Industry case studies are used throughout the book to illustrate possible applications and scenarios. Packaging for Sustainability draws on the expertise of researchers and industry practitioners to provide information on business benefits, environmental issues and priorities, environmental evaluation tools, design for environment, marketing strategies, and challenges for the future.

  18. Packaged die heater

    Science.gov (United States)

    Spielberger, Richard; Ohme, Bruce Walker; Jensen, Ronald J.

    2011-06-21

    A heater for heating packaged die for burn-in and heat testing is described. The heater may be a ceramic-type heater with a metal filament. The heater may be incorporated into the integrated circuit package as an additional ceramic layer of the package, or may be an external heater placed in contact with the package to heat the die. Many different types of integrated circuit packages may be accommodated. The method provides increased energy efficiency for heating the die while reducing temperature stresses on testing equipment. The method allows the use of multiple heaters to heat die to different temperatures. Faulty die may be heated to weaken die attach material to facilitate removal of the die. The heater filament or a separate temperature thermistor located in the package may be used to accurately measure die temperature.

  19. Formulation of a mmaA4 gene deletion mutant of Mycobacterium bovis BCG in cationic liposomes significantly enhances protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Steven C Derrick

    Full Text Available A new vaccination strategy is urgently needed for improved control of the global tuberculosis (TB epidemic. Using a mouse aerosol Mycobacterium tuberculosis challenge model, we investigated the protective efficacy of a mmaA4 gene deletion mutant of Mycobacterium bovis BCG (ΔmmaA4BCG formulated in dimethyl dioctadecyl ammonium bromide (DDA - D(+ trehalose 6,6 dibenenate (TDB (DDA/TDB adjuvant. In previous studies, deletion of the mmaA4 gene was shown to reduce the suppression of IL-12 production often seen after mycobacterial infections. While the non-adjuvanted ΔmmaA4BCG strain did not protect mice substantially better than conventional BCG against a tuberculous challenge in four protection experiments, the protective responses induced by the ΔmmaA4BCG vaccine formulated in DDA/TDB adjuvant was consistently increased relative to nonadjuvanted BCG controls. Furthermore, the ΔmmaA4BCG-DDA/TDB vaccine induced significantly higher frequencies of multifunctional (MFT CD4 T cells expressing both IFNγ and TNFα (double positive or IFNγ, TNFα and IL-2 (triple positive than CD4 T cells derived from mice vaccinated with BCG. These MFT cells were characterized by having higher IFNγ and TNFα median fluorescence intensity (MFI values than monofunctional CD4 T cells. Interestingly, both BCG/adjuvant and ΔmmaA4BCG/adjuvant formulations induced significantly higher frequencies of CD4 T cells expressing TNFα and IL-2 than nonadjuvanted BCG or ΔmmaA4BCG vaccines indicating that BCG/adjuvant mixtures may be more effective at inducing central memory T cells. Importantly, when either conventional BCG or the mutant were formulated in adjuvant and administered to SCID mice or immunocompromised mice depleted of IFNγ, significantly lower vaccine-derived mycobacterial CFU were detected relative to immunodeficient mice injected with non-adjuvanted BCG. Overall, these data suggest that immunization with the ΔmmaA4BCG/adjuvant formulation may be an effective

  20. Efeito do Mycobacterium bovis BCG, lipopolissacarideo bacteriano e hidrocortisona no desenvolvimento de imunidade ao Plasmodium berghei em camundongos

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1986-02-01

    Full Text Available Mycobacterium bovis (BCG aumenta significantemente o desenvolvimento da imunidade nos camundongos CFW, C57BL/6, C57BL/l0ScN e BALB/c (Nu/+ para os estágios eritrocitos do Plasmodium berghei. Camundongos tratados com BCG requerem menos ciclos de infecção com P. berghei e cura pelo Fansidar (pirimetamina + sulfadoxina para desenvolverem imunidade sólida a este parasita do que os controles. Contudo, os animais que receberam BCG 30 dias antes do início da imunização evidenciaram uma perda precoce da imunidade adquirida para o P. berghei, quando comparado com os animais que receberam BCG 14 dias antes ou que não receberam BCG. Assim, sendo, o BCG aumentada a indução na resposta imune do hospedeiro ao P. berghei no curso de infecções subseqüentes. O tratamento de camundongos CFW, BALB/c e C57BL/6 com lipopolissacarídeo bacteriano ou hidrocortisona faz com que os animais requeiram um número maior de ciclos de infecção e cura para tornarem-se imunes ao P. berghei que os controles. O tratamento dos camundongos C57BL/10ScN com hidrocortisona aboliu completamente a sua habilidade de sobrevida subseqüentes a ciclos de infecção com P. berghei e cura pelo Fansidar.

  1. Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper

    2017-01-01

    , determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio......The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets...... (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4(+) T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8(+) T cells), and reduced proportions of late differentiated CD4(+) T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4(+) T cells at 13 months (GMR = 0...

  2. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Elzein, Fatehi; Albogami, Nada; Saad, Mustafa; El Tayeb, Nazik; Alghamdi, Abdullah; Elyamany, Ghaleb

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) remains a first-line treatment for superficial transitional cell carcinoma of the bladder. Although its use is relatively safe, severe complications such as granulomatous hepatitis, osteomyelitis, pneumonitis, and sepsis occur in few patients. Complications of intravesical instillation of BCG can be local or systemic, with early or late presentation. Here, we report an 88-year-old man who developed fever, rigors, and episodes of syncope following fourth intravesical BCG instillation for the treatment of superficial transitional cell carcinoma of the bladder. Pancytopenia, disseminated intravascular coagulation, ground glass appearance on computerized tomography of the chest scan in addition to multiple bone marrow granulomas, suggested the diagnosis of disseminated BCG infection. All these features recovered on antituberculosis treatment. Our case study highlights the importance of early recognition and prompt treatment of patients with disseminated BCG infection following intravesical instillation. Although isolation of mycobacterium is desirable to make the diagnosis, it is not unusual to have negative smears and cultures and this should not be used to dismiss the possibility of BCG infection.

  4. Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

    Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood.......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child.......Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood....... My focus for this project is decision making. Method: During the next year all parents planning to give birth at Kolding Hospital will be offered inclusion in the study . In the 2nd/3rd trimester they will receive a letter with information on the study and afterward the local Ph...

  5. Plasma physics plotting package

    International Nuclear Information System (INIS)

    Hyman, D.H.

    1981-02-01

    We describe a package of plotting routines that do up to six two- or three-dimensional plots on a frame with minimal loss of resolution. The package now runs on a PDP-10 with PLOT-10 TCS primitives and on a Control Data Corporation-7600 and a Cray-1 with TV80LIB primitives on the National Magnetic Fusion Energy Computer Center network. The package is portable to other graphics systems because only the primitive plot calls are used from the underlying system's graphics package

  6. User friendly packaging

    DEFF Research Database (Denmark)

    Geert Jensen, Birgitte

    2010-01-01

    “User-friendly Packaging” aims to create a platform for developing more user-friendly packaging. One intended outcome of the project is a guideline that industry can use in development efforts. The project also points the way for more extended collaboration between companies and design researchers. How...... can design research help industry in packaging innovation?......Most consumers have experienced occasional problems with opening packaging. Tomato sauce from the tinned mackerel splattered all over the kitchen counter, the unrelenting pickle jar lid, and the package of sliced ham that cannot be opened without a knife or a pair of scissors. The research project...

  7. User friendly packaging

    DEFF Research Database (Denmark)

    Geert Jensen, Birgitte

    2010-01-01

    Most consumers have experienced occasional problems with opening packaging. Tomato sauce from the tinned mackerel splattered all over the kitchen counter, the unrelenting pickle jar lid, and the package of sliced ham that cannot be opened without a knife or a pair of scissors. The research project...... “User-friendly Packaging” aims to create a platform for developing more user-friendly packaging. One intended outcome of the project is a guideline that industry can use in development efforts. The project also points the way for more extended collaboration between companies and design researchers. How...... can design research help industry in packaging innovation?...

  8. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie

    2016-01-01

    MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  9. Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

    Science.gov (United States)

    Norouzi, Sayna; Aghamohammadi, Asghar; Mamishi, Setareh; Rosenzweig, Sergio D.; Rezaei, Nima

    2016-01-01

    Summary Primary immunodeficiency diseases (PIDs) are a group of inherited disorders, characterized by defects of the immune system predisposing individuals to variety of manifestations, including recurrent infections and unusual vaccine complications. There are a number of PIDs prone to Bacillus Calmette-Guérin (BCG) complications. This review presents an update on our understanding about the BCGosis-susceptible PIDs, including severe combined immunodeficiency, chronic granulomatous disease, and Mendelian susceptibility to mycobacterial diseases. PMID:22430715

  10. IFN Alfa-2B and BCG Therapy Is An Effective Method In Superficial Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmet Ozdemir

    2012-04-01

    Full Text Available Aim: The initial therapy for superficial bladder carcinoma is the transurethral resection of the tumor. In spite of successful resections, there are 60-79% recurrence and 15% progression rates. Additional therapies are suggested for the treatment of superficial bladder carcinoma. We compared the efficacy of interferon alfa-2b monotherapy with interferon alfa-2b plus Bacillus Calmette Guerin (BCG combination therapy with urine interleukin (IL 2, 6 and 10 levels of patients with superficial bladder carcinoma. Material and Method: The patients who underwent TUR-BT for superficial bladder tumor (pathological staging Ta-T1 between 2004 and 2007 at our hospital included in this prospective study. Intravesical immunotherapy was administered once a week for 6 weeks and there after a month for 6 months, starting 4 weeks after TUR-BT. IL levels were measured. Results: IL-2, IL-6 and IL- 10 levels in urine samples were taken at 2nd and 4th hours of intravesical therapy. A statistically significant difference was observed between mean urine IL-2 levels of patients treated with IFN%u03B1-2b monotherapy and IFN%u03B1- 2b plus BCG combination both at 2nd and 4th hours. (p=0.05 In IFN%u03B1-2b plus BCG combination group, there was a statistical significant difference between stages regarding IL-2 and IL-6 levels (p=0.05. Among patients with G3 tumors, IL-2 levels were higher at 2 and 4 hours (p=0.05 but there was no significant difference in IL-6 and IL-10 levels in this group of patients regardless of intravesical therapy received (p=0.05. Discussion: IFN%u03B1-2b and BCG combination therapy is a reliable and effective therapy in the management of superficial bladder tumors.

  11. Doença de Pott após tratamento intravesical com Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Samaher Tannira

    2016-03-01

    Full Text Available Resumo: Os autores descrevem um caso de osteomielite da coluna vertebral a M. Bovis BCG num doente de 83 anos, com história prévia de carcinoma urotelial da bexiga, submetido a ressecção trans-uretral e imunoterapia com BCG intravesical durante 3 anos. Cinco anos após realização desta terapêutica, o doente desenvolveu quadro de paraparésia progressiva, tendo realizado ressonância magnética que revelou lesão osteolítica ao nível de D10 e D11, sugestiva de infiltração secundária/infecciosa. Foi submetido a laminectomia de D10 a L1 e vertebroplastia D11 a D12. O exame directo foi positivo para micobactérias e a microscopia da lesão osteolítica dorsal identificou inflamação granulomatosa com presença de células gigantes, tendo iniciado terapêutica com Isoniazida, Rifampicina, Pirazinamida e Etambutol, com melhoria clínica. Abstract: The authers describe a case of M. bovis BCG vertebral osteomyelitis in a patient of 83 years with a previous history of urothelial bladder carcinoma, underwent trans-urethral resection and intravesical BCG immunotherapy for 3 years. Five years post-treatment, the patient developed progressive paraparesis. Magnetic resonance imaging revealed lytic lesion at the level of D10 and D11, suggestive of secondary/infectious infiltration. Laminectomy of D10-L1 and vertebroplasty of D11-D12 has been performed. Direct smear examination for mycobacteria showed to be positive. Microscopy of dorsal osteolytic lesion identified granulomatous inflammation with giant cells. The patient showed clinical improvment after treatment with isoniazid, rifampicin, pyrazinamide and ethambutol.

  12. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  13. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

    2003-07-01

    Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  14. Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Julieti Huch Buss

    2018-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette–Guerin (BCG remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1 controlling drug release for extended time frames, (2 combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3 reducing systemic side effects, (4 increasing bioavailability, (5 and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

  15. Effect of BCG vaccine on peritoneal endometriotic implants in a rat model of endometriosis.

    Science.gov (United States)

    Itil, Ismail Mete; Cirpan, Teksin; Akercan, Fuat; Gamaa, Akram; Kazandi, Mert; Kazandi, Ali Can; Yildiz, Pinar Solmaz; Askar, Niyazi

    2006-02-01

    To investigate the effect of Bacillus Calmette-Guerin (BCG) vaccine on peritoneal implantation of endometrial tissue in rats. Forty sexually mature virgin Wistar albino rats weighing 190-200 g were randomly assigned (double blind) to two groups. The rats in the first group were vaccinated with 0.1 mL BCG and those in the second group were injected with 0.1 mL saline into the tail, intracutaneously. All the rats underwent median laparotomy after 4 weeks of vaccination or injection. The right uterine horn was excised, and the two samples of endometrial tissue dissected from myometrium were implanted on each side of peritoneum at the 2 cm lateral line of the median laparotomy incision. The implanted peritoneal segments were excised after 8 weeks of laparotomy. The tissue samples were accepted, histologically, as endometriosis when both glands and stroma of endometrial tissue were seen in sections. Thirty-six implants from the study group and 34 implants from the control group were obtained. Ten and 23 implants were accepted as endometriosis in the study and control group, respectively. The number of endometriotic foci were significantly lower in the study group than in the control group (P = 0.01). Stimulation of the cellular immune response with BCG vaccine could exert an inhibitory effect on ectopic endometriotic implants.

  16. Quality control and safety assessment of BCG vaccines in the post-genomic era

    Science.gov (United States)

    Stefanova, Tzvetelina

    2014-01-01

    A hundred and five years ago, Albert Calmette and Camille Guérin began a daunting task, which is unmatched even today, that led to the most widely used vaccine in human history. Despite a century of scientific advances, BCG (an acronym for Bacillus Calmette–Guérin) remains the only vaccine for prevention of tuberculosis. Due to the fact that the use of BCG vaccines will continue, either as a stand-alone or as a prime vaccine in prime-boost immunization strategies, the World Health Organization (WHO) has underlined the necessity for further work toward better characterization, evaluation and quality control of the BCG vaccine, taking into account recent advances in genetics and molecular biology. The potential benefit of such improved characterization could be addressed to better and easier differentiation between sub-strains used by different manufacturers. It may help to ensure consistency of production in terms of genetic stability and it may also help the clinical evaluation of new antituberculosis vaccines. Last but not least, the state-of-the-art technologies could facilitate the quality control performed by the manufacturers and by National Control Authorities as well. PMID:26019525

  17. [Our experience with 1 mg BCG vaccine instillation in T1 stage cancer of the bladder].

    Science.gov (United States)

    Rivera, P; Orio, M; Hinostroza, J; Venegas, P; Pastor, P; Gorena, M; Lagos, M; Pinochet, R

    1999-10-01

    We studied 67 patients with bladder cancer in stage T1, with terminated BCG treatment and in pursuit. No stage Ta neither carcinoma in situ was included. The protocol was: beginning of treatment upon retiring vesical catheter, instilation of 1 mg of liofilized BCG vaccine (16 x 10(6) bacilles) in 40-50 ml of intravesical saline solution. A weekly instilation during the first month. An instilation each 15 days during the second and third month and one monthly until complete 12 months of treatment. Also was carried out an study of T lymphocites and cytokines. The average followup of the 67 patients treated was 51.3 months. 17 patients relapses (25.4%). A 33% were grade 3 and 27% grade 2. Like complications there was a case of inguinal TBC adenititis, 2 TBC prostatitis, 2 TBC cistitis and 5 cases of slight disuric syndrome. The study of subpopulations of lymphocites in peripheral blood demonstrated a significant increase of CD3 and CD4/CD8 ratio. The interleukin 2 measurement in serum also increased significantly after the BCG instilations. Our protocol gets similar results to the higher doses, but with minimal complications diminishing the relapses of the tumors in stage T1. A monthly maintenance dose would help to maintain immunity.

  18. Is tuberculin testing before BCG vaccination necessary for children over three months of age?

    LENUS (Irish Health Repository)

    Hennessy, B

    2008-03-01

    In July 2007 Irish national policy changed such that children aged 3 months to 6 years no longer routinely require tuberculin (Mantoux) skin testing prior to BCG vaccination. Previous to that a tuberculin test was required in all children in this age group pre vaccination. While the previous policy was in place this study was conducted to assess the value of this test. The observation that children are frightened by the test (an injection into the skin) prompted the study. The author conducted a retrospective study of the results of 1,854 tuberculin tests performed as a prerequisite to BCG vaccination and found that only 0.7% of children had a positive test result (induration > 5mm). None of 107 children < 6 years of age tested positive. Those > 12 years were more likely to test positive than younger children (1.09% vs 0.4% respectively, p < 0.05). This study suggests that testing young children before BCG vaccination has a low yield of positive results and adds little to the detection of latent or active TB.

  19. Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance.

    Science.gov (United States)

    Cernuschi, Tania; Malvolti, Stefano; Nickels, Emily; Friede, Martin

    2018-01-25

    Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014-2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management. Copyright © 2017. Published by Elsevier Ltd.

  20. Expression of Cathepsin S in BCG converts it into a pro-apoptotic and highly immunogenic strain.

    Science.gov (United States)

    Lau, Alice; Singh, Vijender; Soualhine, Hafid; Hmama, Zakaria

    2017-04-11

    BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation. One of these studies revealed that defect in antigen presentation is largely due to down-regulation of the cysteine protease Cathepsin S (CatS), which prevents MHC II molecule maturation and proper antigen peptide loading. Recent studies also suggested a potential role for cysteine proteases in the regulation of apoptosis, a key cellular process used by the macrophage to (i) contain and process ingested bacteria and (ii) facilitate cross-talk antigen presentation between the macrophage and dendritic cells. To reverse the phenotype of vaccine-mediated macrophage attenuation, we engineered a novel BCG strain that expresses and secretes active CatS (rBCG-CatS) to examine its pro-apoptotic properties in vitro, and subsequently, immunogenicity in mice. Transcriptomic profiling of macrophages infected with rBCG-CatS, but not BCG, revealed upregulation of key pro-apoptotic genes and downregulation of anti-apoptotic genes, which were further confirmed by RT-qPCR analyses of expression of selected genes. Macrophages infected with rBCG-CatS undergo apoptosis as indicated by increased levels of annexin V staining and intracellular caspase-3 cleavage. Consistent with these findings, mice vaccinated with rBCG-CatS showed increased antigen-specific CD4 + T-cell responses, as well as enhanced cytokine production and proliferation in CD4 + upon ex vivo re-stimulation. Collectively, this study shows that a pro-apoptotic BCG strain alleviates adverse traits of the wild

  1. The BINSYN Program Package

    Directory of Open Access Journals (Sweden)

    Albert P. Linnell

    2012-06-01

    Full Text Available The BINSYN program package, recently expanded to calculate synthetic spectra of cataclysmic variables, is being further extended to include synthetic photometry of ordinary binary stars in addition to binary stars with optically thick accretion disks. The package includes a capability for differentials correction optimization of eclipsing binary systems using synthetic photometry.

  2. Nutrition. Learning Activity Package.

    Science.gov (United States)

    Lee, Carolyn

    This learning activity package on nutrition is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, a list of definitions, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  3. WASTE PACKAGE TRANSPORTER DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    D.C. Weddle; R. Novotny; J. Cron

    1998-09-23

    The purpose of this Design Analysis is to develop preliminary design of the waste package transporter used for waste package (WP) transport and related functions in the subsurface repository. This analysis refines the conceptual design that was started in Phase I of the Viability Assessment. This analysis supports the development of a reliable emplacement concept and a retrieval concept for license application design. The scope of this analysis includes the following activities: (1) Assess features of the transporter design and evaluate alternative design solutions for mechanical components. (2) Develop mechanical equipment details for the transporter. (3) Prepare a preliminary structural evaluation for the transporter. (4) Identify and recommend the equipment design for waste package transport and related functions. (5) Investigate transport equipment interface tolerances. This analysis supports the development of the waste package transporter for the transport, emplacement, and retrieval of packaged radioactive waste forms in the subsurface repository. Once the waste containers are closed and accepted, the packaged radioactive waste forms are termed waste packages (WP). This terminology was finalized as this analysis neared completion; therefore, the term disposal container is used in several references (i.e., the System Description Document (SDD)) (Ref. 5.6). In this analysis and the applicable reference documents, the term ''disposal container'' is synonymous with ''waste package''.

  4. NRF TRIGA packaging

    International Nuclear Information System (INIS)

    Clements, M.D.

    1995-11-01

    Training Reactor Isotopes, General Atomics (TRIGA reg-sign) Reactors are in use at four US Department of Energy (DOE) complex facilities and at least 23 university, commercial, or government facilities. The development of the Neutron Radiography Facility (NRF) TRIGA packaging system began in October 1993. The Hanford Site NRF is being shut down and requires an operationally user-friendly transportation and storage packaging system for removal of the TRIGA fuel elements. The NRF TRIGA packaging system is designed to remotely remove the fuel from the reactor and transport the fuel to interim storage (up to 50 years) on the Hanford Site. The packaging system consists of a cask and an overpack. The overpack is used only for transport and is not necessary for storage. Based upon the cask's small size and light weight, small TRIGA reactors will find it versatile for numerous refueling and fuel storage needs. The NRF TRIGA packaging design also provides the basis for developing a certifiable and economical packaging system for other TRIGA reactor facilities. The small size of the NRF TRIGA cask also accommodates placing the cask into a larger certified packaging for offsite transport. The Westinghouse Hanford Company NRF TRIGA packaging, as described herein can serve other DOE sites for their onsite use, and the design can be adapted to serve university reactor facilities, handling a variety of fuel payloads

  5. Grooming. Learning Activity Package.

    Science.gov (United States)

    Stark, Pamela

    This learning activity package on grooming for health workers is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  6. Evaluation of immunogenicity and protective efficacy elicited by Mycobacterium bovis BCG overexpressing Ag85A protein against Mycobacterium tuberculosis aerosol infection

    Directory of Open Access Journals (Sweden)

    Zheng Zhong Xu

    2016-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette-Guérin (BCG is currently the only vaccine available against tuberculosis (TB, however, it has various levels of efficacy for preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. The results showed that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, the Ag85A peptide–MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that the rBCG::Ag85A can provide higher but not significantly protective efficacy against Mycobacterium tuberculosis (M. tuberculosis H37Rv infection compared with BCG vaccine. Therefore, our results demonstrated the potential of rBCG::Ag85A as a vaccine candidate against TB.

  7. Studies of monocytopoiesis in patients with malignant disease and after imunostimulation with BCG, using /sup 3/H-thymidine as a DNA-label

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, E.; Meuret, G.; Waldermann, F.; Hoffmann, G.

    1982-04-01

    Monocytopoiesis and blood monocytes were investigated in patients with Hodgkin's disease, non-Hodgkin lymphomas, mycosis fungoides, breast cancer or melanoma. The investigation was carried out before surgery and just before each application of BCG. Monocyte production was increased in untreated patients. Postoperative prophylactic BCG-vaccination gave rise to increased proliferation activity. However monocyte production returned to normal between the 4th and 6th month of BCG immunotherapy. These results indicate that monocytopoiesis is stimulated by human tumors. BCG immunostimulation is able to increase proliferation activity during the first month of treatment only.

  8. Advanced flip chip packaging

    CERN Document Server

    Lai, Yi-Shao; Wong, CP

    2013-01-01

    Advanced Flip Chip Packaging presents past, present and future advances and trends in areas such as substrate technology, material development, and assembly processes. Flip chip packaging is now in widespread use in computing, communications, consumer and automotive electronics, and the demand for flip chip technology is continuing to grow in order to meet the need for products that offer better performance, are smaller, and are environmentally sustainable. This book also: Offers broad-ranging chapters with a focus on IC-package-system integration Provides viewpoints from leading industry executives and experts Details state-of-the-art achievements in process technologies and scientific research Presents a clear development history and touches on trends in the industry while also discussing up-to-date technology information Advanced Flip Chip Packaging is an ideal book for engineers, researchers, and graduate students interested in the field of flip chip packaging.

  9. RH Packaging Operations Manual

    International Nuclear Information System (INIS)

    Washington TRU Solutions LLC

    2003-01-01

    This procedure provides operating instructions for the RH-TRU 72-B Road Cask, Waste Shipping Package. In this document, ''Packaging'' refers to the assembly of components necessary to ensure compliance with the packaging requirements (not loaded with a payload). ''Package'' refers to a Type B packaging that, with its radioactive contents, is designed to retain the integrity of its containment and shielding when subject to the normal conditions of transport and hypothetical accident test conditions set forth in 10 CFR Part 71. Loading of the RH 72-B cask can be done two ways, on the RH cask trailer in the vertical position or by removing the cask from the trailer and loading it in a facility designed for remote-handling (RH). Before loading the 72-B cask, loading procedures and changes to the loading procedures for the 72-B cask must be sent to CBFO at sitedocuments at wipp.ws for approval

  10. Oral vaccination of badgers (Meles meles) against tuberculosis: comparison of the protection generated by BCG vaccine strains Pasteur and Danish.

    Science.gov (United States)

    Murphy, Denise; Costello, Eamon; Aldwell, Frank E; Lesellier, Sandrine; Chambers, Mark A; Fitzsimons, Tara; Corner, Leigh A L; Gormley, Eamonn

    2014-06-01

    Vaccination of badgers by the subcutaneous, mucosal and oral routes with the Pasteur strain of Mycobacterium bovis bacille Calmette-Guérin (BCG) has resulted in significant protection against experimental infection with virulent M. bovis. However, as the BCG Danish strain is the only commercially licensed BCG vaccine for use in humans in the European Union it is the vaccine of choice for delivery to badger populations. As all oral vaccination studies in badgers were previously conducted using the BCG Pasteur strain, this study compared protection in badgers following oral vaccination with the Pasteur and the Danish strains. Groups of badgers were vaccinated orally with 10(8) colony forming units (CFU) BCG Danish 1331 (n = 7 badgers) or 10(8) CFU BCG Pasteur 1173P2 (n = 6). Another group (n = 8) served as non-vaccinated controls. At 12 weeks post-vaccination, the animals were challenged by the endobronchial route with 6 × 10(3) CFU M. bovis, and at 15 weeks post-infection, all of the badgers were euthanased. Vaccination with either BCG strain provided protection against challenge compared with controls. The vaccinated badgers had significantly fewer sites with gross pathology and significantly lower gross pathological severity scores, fewer sites with histological lesions and fewer sites of infection, significantly lower bacterial counts in the thoracic lymph node, and lower bacterial counts in the lungs than the control group. No differences were observed between either of the vaccine groups by any of the pathology and bacteriology measures. The ELISPOT analysis, measuring production of badger interferon - gamma (IFN-γ), was also similar across the vaccinated groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. iNOS EXPRESSION AND NO PRODUCTION CONTRIBUTE TO THE DIRECT EFFECTS OF BCG ON UROTHELIAL CARCINOMA CELL BIOLOGY

    Science.gov (United States)

    Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, YanLi; Kalyanaraman, Balaraman; See, William A.

    2018-01-01

    OBJECTIVES Evidence suggests that oxidative stress occurring as a consequence of inducible nitric oxide synthase/nitric oxide (iNOS/NO) contributes to the biologic effects of Bacille Calmette Guérin (BCG). Objective of the current study is to examine iNOS expression, NO production and the biologic impact of NO, on established intermediate end points for the human urothelial carcinoma cell response to BCG. MATERIALS AND METHODS Quantitative rt-PCR and real time measurement of NO was used to assess iNOS and NO production respectively, in two human urothelial carcinoma (UC) cell lines, in response to BCG. The effect of blocking NO production using the specific iNOS inhibitor 1400W was determined for multiple intermediate end points characterizing BCGs direct effects on tumor cell biology. Activation of NF-κB and NRF2 signaling pathways, transactivation of genes including p21, CD54, IL6, IL8, CXCL1, CXCL3, CCL20 and cytotoxicity as measured by vital dye exclusion, lactate dehydrogenase (LDH) release and MTT assay were measured in response to BCG with and without iNOS inhibition. RESULTS Exposure of UC cells to BCG significantly increased both iNOS expression and NO production. Inhibition of iNOS activity with 1400W significantly inhibited BCG’s direct biologic effect on UC cells for all of the end points evaluated. CONCLUSIONS iNOS expression, NO production and the associated oxidative stress play a central role in the response of UC cells to BCG exposure. Manipulation of oxidative stress may afford an opportunity to enhance the antitumor effects of BCG. PMID:24054867

  12. Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

    Science.gov (United States)

    Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

    2012-01-01

    Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by

  13. Comparative tuberculosis (TB prevention effectiveness in children of Bacillus Calmette-Guérin (BCG vaccines from different sources, Kazakhstan.

    Directory of Open Access Journals (Sweden)

    Michael Favorov

    Full Text Available BACKGROUND: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. METHODS/FINDINGS: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan, the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. LIMITATIONS: Potential limitations included considerations that 1 the methodology used was retrospective, 2 multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3 most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4 small variations in reported population TB burden could have affected relative risk of exposure for cohorts. CONCLUSIONS/SIGNIFICANCE: All three BCG vaccines evaluated were protective against TB, and prevention effectiveness

  14. Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guérin (BCG) vaccines from different sources, Kazakhstan.

    Science.gov (United States)

    Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

    2012-01-01

    Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration

  15. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bappaditya Dey

    Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

  16. BCG immune activation reduces growth and angiogenesis in an in vitro model of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Sánchez-Rodríguez, Carolina; Cruces, Keyliz Peraza; Riestra Ayora, Juan; Martín-Sanz, Eduardo; Sanz-Fernández, Ricardo

    2017-11-07

    Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide and is associated with poor survival and significant treatment morbidity. The immune profile in patients with HNSCC is immunosuppressive and presents cytokine-mediated adaptive immune responses, triggered apoptosis of T cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin (BCG) immunotherapy has been used successfully as a treatment for several types of cancer. In the present study, we sought to determine the antitumor effect of soluble mediators from peripheral blood mononuclear immune cells (PBMCs) activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth using FaDu hypopharynx carcinoma squamous cells. BCG activation of PBMCs led to an increase in CD4+ and CD8+ lymphocyte subsets concomitant with an elevation in the levels of the antitumor cytokines IL-6, TNF-α and IFN-γ, and a EGFR in FaDu cells. In addition, coculture with BCG-activated PBMCs reduced FaDu proliferation and increased cytotoxicity and apoptosis in parallel with an increase in caspase-3 activity and p53 expression. Finally, conditioned medium from BCG-activated PBMCs reduced the levels of the angiogenic factors vascular endothelial growth factor and angiopoietin-2 produced by human aortic endothelial cells (HAECs), and inhibited their proliferation and differentiation into capillary-like structures. Taken together, these results demonstrate that BCG vaccination induces antitumor responses in an HNSCC in vitro model and suggest that the BCG vaccine could be an effective alternative therapy for the treatment of HNSCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial.

    Science.gov (United States)

    Pereira, Susan M; Barreto, Mauricio L; Pilger, Daniel; Cruz, Alvaro A; Sant'Anna, Clemax; Hijjar, Miguel A; Ichihara, Maria Y; Santos, Andreia C; Genser, Bernd; Rodrigues, Laura C

    2012-04-01

    Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3-66·7) per 100,000 person-years in the BCG vaccination group and 72·7 (62·8-86·8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school

  18. Packaging Concerns/Techniques for Large Devices

    Science.gov (United States)

    Sampson, Michael J.

    2009-01-01

    This slide presentation reviews packaging challenges and options for electronic parts. The presentation includes information about non-hermetic packages, space challenges for packaging and complex package variations.

  19. Packaging Printing Today

    Directory of Open Access Journals (Sweden)

    Stanislav Bolanča

    2015-12-01

    Full Text Available Printing packaging covers today about 50% of all the printing products. Among the printing products there are printing on labels, printing on flexible packaging, printing on folding boxes, printing on the boxes of corrugated board, printing on glass packaging, synthetic and metal ones. The mentioned packaging are printed in flexo printing technique, offset printing technique, intaglio halftone process, silk – screen printing, ink ball printing, digital printing and hybrid printing process. The possibilities of particular printing techniques for optimal production of the determined packaging were studied in the paper. The problem was viewed from the technological and economical aspect. The possible printing quality and the time necessary for the printing realization were taken as key parameters. An important segment of the production and the way of life is alocation value and it had also found its place in this paper. The events in the field of packaging printing in the whole world were analyzed. The trends of technique developments and the printing technology for packaging printing in near future were also discussed.

  20. Hermeticity of electronic packages

    CERN Document Server

    Greenhouse, Hal

    2000-01-01

    This is a book about the integrity of sealed packages to resist foreign gases and liquids penetrating the seal or an opening (crack) in the package-especially critical to the reliability and longevity of electronics. The author explains how to predict the reliability and the longevity of the packages based on leak rate measurements and the assumptions of impurities. Non-specialists in particular will benefit from the author's long involvement in the technology. Hermeticity is a subject that demands practical experience, and solving one problem does not necessarily give one the background to so

  1. Hermeticity of electronic packages

    CERN Document Server

    Greenhouse, Hal; Romenesco, Bruce

    2011-01-01

    This is a book about the integrity of sealed packages to resist foreign gases and liquids penetrating the seal or an opening (crack) in the packageùespecially critical to the reliability and longevity of electronics. The author explains how to predict the reliability and the longevity of the packages based on leak rate measurements and the assumptions of impurities. Non-specialists in particular will benefit from the author's long involvement in the technology. Hermeticity is a subject that demands practical experience, and solving one problem does not necessarily give one the background to so

  2. Safety Analysis Report - Packages, 9965, 9968, 9972-9975 Packages

    International Nuclear Information System (INIS)

    Blanton, P.

    2000-01-01

    This Safety Analysis Report for Packaging (SARP) documents the analysis and testing performed on four type B Packages: the 9972, 9973, 9974, and 9975 packages. Because all four packages have similar designs with very similar performance characteristics, all of them are presented in a single SARP. The performance evaluation presented in this SARP documents the compliance of the 9975 package with the regulatory safety requirements. Evaluations of the 9972, 9973, and 9974 packages support that of the 9975. To avoid confusion arising from the inclusion of four packages in a single document, the text segregates the data for each package in such a way that the reader interested in only one package can progress from Chapter 1 through Chapter 9. The directory at the beginning of each chapter identifies each section that should be read for a given package. Sections marked ''all'' are generic to all packages

  3. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Angela Liao

    Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

  4. In vivo evaluation of the efficacy of Sophora moorcroftiana alkaloids in combination with Bacillus Calmette-Guérin (BCG) treatment for cystic echinococcosis in mice.

    Science.gov (United States)

    Zhang, G; Wang, J; Luo, Y; Yuan, M; Gao, Q; Gao, H; Song, X; Shi, Y; Dong, K; Ma, X

    2017-10-24

    Human cystic echinococcosis is a widespread, chronic, endemic, helminthic zoonosis caused by larval tapeworms of the species Echinococcus granulosus. At present, there is no rational and effective therapy for patients with echinococcosis. The present study evaluated whether the combination of alkaloids from Sophora moorcroftiana seeds (SMSa2) and Bacillus Calmette-Guérin (BCG) was effective in the treatment of experimental echinococcosis. After 20 weeks of secondary infection with protoscoleces, mice were randomly allocated to five groups and treated for 6 weeks by daily intragastric administration of albendazole (ABZ, 100 mg/kg), SMSa2 (100 mg/kg), BCG (abdominal subcutaneous injection at 5 × 106 CFU), SMSa2 + BCG (100 mg/kg SMSa2 and 5 × 106 CFU BCG) or normal saline (untreated group), respectively. The results indicated a significant reduction in the weight of hydatid cysts in the SMSa2 + BCG group compared with the untreated, SMSa2 and BCG groups. The rate of inhibition of hydatid cyst growth in the SMSa2 + BCG group (76.1%) was obviously increased compared with that in the SMSa2 (25.7%) and BCG (26.6%) groups, respectively. Compared with the untreated control, the SMSa2 + BCG group showed a non-significant increase in serum interleukin-4 (IL-4). Furthermore, the serum levels of interferon-γ (IFN-γ) between the untreated and SMSa2 + BCG groups were not statistically different. Therefore, the combination of alkaloids from S. moorcroftiana seeds and BCG can reduce cyst burden and is an effective therapeutic regimen against echinococcosis.

  5. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System

    Science.gov (United States)

    Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

    2015-01-01

    Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine. PMID:26716832

  6. Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

    Science.gov (United States)

    Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

    2016-04-01

    Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection.

    Science.gov (United States)

    Zhang, Ming; Dong, Chunsheng; Xiong, Sidong

    2017-04-03

    Tuberculosis (TB) remains a major health problem worldwide, and the development of effective vaccines is urgently needed. Vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as primer and modified vaccinia virus Ankara strain expressing the mycobacterial antigen Ag85A (MVA85A) as booster may increase the protective efficacy of BCG. In addition, vaccination with the recombinant viral vaccine vesicular stomatitis virus (VSV)-846 (Rv3615c, Mtb10.4, and Rv2660c) can elicit a remarkable T-cell-mediated immune response and provide an effective long-term protection after the BCG challenge. In this study, we used VSV-846 to boost BCG and evaluated its immunogenicity in BALB/c mice. In this prime-boost approach, boosting with VSV-846 significantly enhanced IFN-γ CD4 T cell responses, which are crucial for anti-TB immune responses. Moreover, VSV-846 boosting significantly reduced pathology compared with mock vaccination, and decreased the bacterial loads in lung tissues compared with BCG or VSV-846 vaccination alone. The analysis of vaccine-induced immunity identified that polyfunctional T cells might contribute to the enhanced protection by VSV-846 boosting. This study proved that viral booster VSV-846 in mice improved the protection against mycobacteria infection, which could be helpful in designing an efficient vaccination strategy against TB in humans.

  8. Boosting BCG with inert spores improves immunogenicity and induces specific IL-17 responses in a murine model of bovine tuberculosis.

    Science.gov (United States)

    Garcia-Pelayo, M Carmen; Kaveh, Daryan A; Sibly, Laura; Webb, Paul R; Bull, Naomi C; Cutting, Simon M; Hogarth, Philip J

    2016-05-01

    Tuberculosis (TB) remains a global pandemic, in both animals and man, and novel vaccines are urgently required. Heterologous prime-boost of BCG represents a promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be an ideal vaccination strategy against bovine TB (bTB), but respiratory vaccination presents a technical challenge in cattle. Inert bacterial spores represent an attractive vaccine vehicle. Therefore we evaluated whether parenterally administered spores are efficacious when used as a BCG boost in a murine model of immunity against Mycobacterium bovis. Here we report the use of heat-killed, TB10.4 adsorbed, Bacillus subtilis spores delivered via subcutaneous injection to boost immunity primed by BCG. We demonstrate that this approach improves the immunogenicity of BCG. Interestingly, this associated with substantial boosting of IL-17 responses; considered to be important in protective immunity against TB. These data demonstrate that parenteral delivery of spores represents a promising vaccine vehicle for boosting BCG, and identifies potential for optimisation for use as a vaccine for bovine TB. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  9. [Examination of protein MPB 70 properties in BCG substrains used for the production of Polish antituberculosis vaccines].

    Science.gov (United States)

    Janaszek, W; Wysokińska, T; Aleksandrowicz, J

    1998-01-01

    The aim of the study was examination of MPB70 protein production by different BCG substrains and testing this protein as reagent in allergenic skin test on BCG vaccinated guinea pigs. Three BCG substrains: Danish 1331 (D), Japanese 172 (J) and Polish BCG Moreau (P) were used for the study. The protein MPB70 received from dr Nagai from Osaka University was used as reference preparation. It has been shown that MPB70 protein of molecular weight about 21,500 Da was present only in BCG Moreau (P) and Japanese (J) substrains. In immunoblotting test monoclonal antibodies reacted additionally with 43,000 Da protein in all tested substrains. We suspect that the detected additional molecule was a dimer of MPB70 protein. The development of skin reactions to MPB70 protein was seen in guinea pigs vaccinated with J and P substrains. The peak of alergy to MPB70 protein was observed 9 weeks after vaccination. In sera of vaccinated animals antibodies against MPB70 protein were detected by ELISA method. The possibility of using MPB70 protein for diagnostic purpose is discussed.

  10. Materials for advanced packaging

    CERN Document Server

    Wong, CP

    2017-01-01

    This second edition continues to be the most comprehensive review on the developments in advanced electronic packaging technologies, with a focus on materials and processing. Recognized experts in the field contribute to 22 updated and new chapters that provide comprehensive coverage on various 3D package architectures, novel bonding and joining techniques, wire bonding, wafer thinning techniques, organic substrates, and novel approaches to make electrical interconnects between integrated circuit and substrates. Various chapters also address advances in several key packaging materials, including: Lead-free solders Flip chip underfills Epoxy molding compounds Conductive adhesives Die attach adhesives/films Thermal interface materials (TIMS) Materials for fabricating embedded passives including capacitors, inductors, and resistors Materials and processing aspects on wafer-level chip scale package (CSP) and MicroElectroMechanical system (MEMS) Contributors also review new and emerging technologies such as Light ...

  11. Informative document packaging waste

    NARCIS (Netherlands)

    Joosten JM; Nagelhout D; Duvoort GL; Weerd M de

    1989-01-01

    This "informative document packaging waste" forms part of a series of "informative documents waste materials". These documents are conducted by RIVM on the instructions of the Direcotrate General for the Environment, Waste Materials Directorate, in behalf of the program of

  12. FLEXIBLE FOOD PACKAGING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains equipment to fabricate and test prototype packages of many types and sizes (e.g., bags, pouches, trays, cartons, etc.). This equipment can...

  13. London 2012 packaging guidelines

    OpenAIRE

    2013-01-01

    These guidelines are intended to provide supplemental advice to suppliers and licensees regarding the provisions of the LOCOG Sustainable Sourcing Code that relate to packaging design and materials selection.

  14. Type B Drum packages

    International Nuclear Information System (INIS)

    Edwards, W.S.

    1995-11-01

    The Type B Drum package is a container in which a single drum containing Type B quantities of radioactive material will be packaged for shipment. The Type B Drum containers are being developed to fill a void in the packaging and transportation capabilities of the US Department of Energy (DOE), as no double containment packaging for single drums of Type B radioactive material is currently available. Several multiple-drum containers and shielded casks presently exist. However, the size and weight of these containers present multiple operational challenges for single-drum shipments. The Type B Drum containers will offer one unshielded version and, if needed, two shielded versions, and will provide for the option of either single or double containment. The primary users of the Type B Drum container will be any organization with a need to ship single drums of Type B radioactive material. Those users include laboratories, waste retrieval facilities, emergency response teams, and small facilities

  15. BCRA R Package

    Science.gov (United States)

    BCRA is an R package that projects absolute risk of invasive breast cancer according to NCI’s Breast Cancer Risk Assessment Tool (BCRAT) algorithm for specified race/ethnic groups and age intervals.

  16. Vaccination of cattle with Danish and Pasteur strains of Mycobacterium bovis BCG induce different levels of IFNgamma post-vaccination, but induce similar levels of protection against bovine tuberculosis.

    Science.gov (United States)

    Wedlock, D Neil; Denis, Michel; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2007-07-15

    A number of studies have demonstrated significant protection of cattle against bovine tuberculosis following vaccination with the Pasteur strain of Mycobacterium bovis bacille Calmete-Guerin (BCG). However, it is unclear if other daughter strains of BCG are as effective, which is an important issue to resolve for a variety of regulatory compliance issues. This study compared the protective immune responses to bovine tuberculosis induced in cattle vaccinated with BCG Danish with those induced by BCG Pasteur. Groups of calves (n=10) were vaccinated with 10(6) colony forming units (CFU) BCG Pasteur prepared from a fresh liquid culture, 10(6) CFU BCG Danish prepared from a fresh liquid culture or 0.4 mg of reconstituted freeze-dried culture of BCG Danish. Another group (n=10) served as non-vaccinated controls. BCG Pasteur induced significantly higher and more sustained levels of bovine purified protein derivative (PPD)-specific gamma interferon (IFN-gamma) in whole-blood cultures following vaccination compared to either fresh culture BCG Danish or freeze-dried BCG Danish. Vaccination with a fresh culture of BCG Pasteur, fresh culture BCG Danish and freeze-dried BCG Danish gave a significant enhancement in three, four and three pathological and microbiological parameters of protection, respectively, compared to the non-vaccinated group. These results demonstrate the Danish strain of BCG is a viable alternative to BCG Pasteur for vaccination of cattle as both strains had similar efficacy and there was little difference between freshly cultured and freeze-dried formulation of BCG Danish. The results also show that post-vaccination antigen-specific IFN-gamma levels in whole blood is not always a reliable indicator of protection against a subsequent virulent challenge.

  17. Electronic Packaging Techniques

    Science.gov (United States)

    1979-01-01

    A characteristic of aerospace system design is that equipment size and weight must always be kept to a minimum, even in small components such as electronic packages. The dictates of spacecraft design have spawned a number of high-density packaging techniques, among them methods of connecting circuits in printed wiring boards by processes called stitchbond welding and parallel gap welding. These processes help designers compress more components into less space; they also afford weight savings and lower production costs.

  18. The ENSDF Java Package

    International Nuclear Information System (INIS)

    Sonzogni, A.A.

    2005-01-01

    A package of computer codes has been developed to process and display nuclear structure and decay data stored in the ENSDF (Evaluated Nuclear Structure Data File) library. The codes were written in an object-oriented fashion using the java language. This allows for an easy implementation across multiple platforms as well as deployment on web pages. The structure of the different java classes that make up the package is discussed as well as several different implementations

  19. Packaging sustainability assessment

    OpenAIRE

    Rubio Peregrina, Silvia

    2015-01-01

    Packaging is an essential part of the majority of products in the actual market. Therefore, packaging design must draw attention to improve its sustainable character in order to satisfy consumers, enhance its environmental performance and keep economic costs to a minimum. Measuring packaging’s sustainability would provide consumers information so as to raise awareness and, moreover, a tool that would help companies to find product weaknesses to be improved. For that purpose, this projec...

  20. CH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Washington TRU Solutions LLC

    2002-03-04

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT Shipping Package, and directly related components. This document complies with the minimum requirements as specified in TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event there is a conflict between this document and the SARP or C of C, the SARP and/or C of C shall govern. C of Cs state: ''each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.'' They further state: ''each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SAR P charges the WIPP Management and Operation (M&O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 CFR 71.11. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. This document details the instructions to be followed to operate, maintain, and test the TRUPACT-II and HalfPACT packaging. The intent of these instructions is to standardize these operations. All users will follow these instructions or equivalent instructions that assure operations are safe and meet the requirements of the SARPs.

  1. Comparative Packaging Study

    Science.gov (United States)

    Perchonok, Michele H.; Oziomek, Thomas V.

    2009-01-01

    Future long duration manned space flights beyond low earth orbit will require the food system to remain safe, acceptable and nutritious. Development of high barrier food packaging will enable this requirement by preventing the ingress and egress of gases and moisture. New high barrier food packaging materials have been identified through a trade study. Practical application of this packaging material within a shelf life test will allow for better determination of whether this material will allow the food system to meet given requirements after the package has undergone processing. The reason to conduct shelf life testing, using a variety of packaging materials, stems from the need to preserve food used for mission durations of several years. Chemical reactions that take place during longer durations may decrease food quality to a point where crew physical or psychological well-being is compromised. This can result in a reduction or loss of mission success. The rate of chemical reactions, including oxidative rancidity and staling, can be controlled by limiting the reactants, reducing the amount of energy available to drive the reaction, and minimizing the amount of water available. Water not only acts as a media for microbial growth, but also as a reactant and means by which two reactants may come into contact with each other. The objective of this study is to evaluate three packaging materials for potential use in long duration space exploration missions.

  2. The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis

    OpenAIRE

    Prados-Rosales, Rafael; Carreño, Leandro J.; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R.; Porcelli, Steven A.; Casadevall, Arturo

    2016-01-01

    Background. Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.

  3. BCG dose reduction by decreasing the instillation frequency: Effects on local Th1/Th2 cytokine responses in a mouse model

    NARCIS (Netherlands)

    de Boer, Elizabeth C.; Rooyakkers, Sietske J.; Schamhart, Denis H. J.; de Reijke, Theo M.; Kurth, Karl-Heinz

    2005-01-01

    Objectives: Based on the requirement of a Th1 immune response for clinical efficacy, and incited by the arbitrary induction scheme, frequent side effects and the empirical approach in improving BCG immunotherapy for superficial bladder cancer, an alternative intravesical BCG treatment schedule for

  4. Serological monitoring of previously treated lepromatous patients during a course of multiple immunotherapy treatments with heat-killed Mycobacterium leprae and BCG

    NARCIS (Netherlands)

    Douglas, J. T.; Hirsch, D. S.; Fajardo, T. T.; Guido, L. S.; Klatser, P. R.

    1990-01-01

    Two-hundred and seventy lepromatous patients who had completed treatment received multiple treatments with heat-killed M. leprae and BCG and were monitored for changes in humoral responses to M. leprae-specific antigens. These patients were divided into four treatment groups: placebo (n = 69); BCG

  5. Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

    Science.gov (United States)

    Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

    2016-12-24

    In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

  6. BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

    DEFF Research Database (Denmark)

    Madura Larsen, Jeppe; Benn, Christine Stabell; Fillie, Yvonne

    2007-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in low-income countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result o...

  7. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah

    2015-10-21

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  8. CYTOKINE PRODUCTION BY THE HUMAN BLADDER-CARCINOMA CELL-LINE T24 IN THE PRESENCE OF BACILLUS-CALMETTE-GUERIN (BCG)

    NARCIS (Netherlands)

    de Reijke, T. M.; Vos, P. C.; de Boer, E. C.; Bevers, R. F.; de Muinck Keizer, W. H.; Kurth, K. H.; Schamhart, D. H.

    1993-01-01

    The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T 24 treated with BCG was investigated. A 24-h treatment of

  9. Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial.

    Science.gov (United States)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper; Hartling, Hans Jacob; Thøstesen, Lisbeth Marianne; Kofoed, Poul-Erik; Stensballe, Lone Graff; Andersen, Andreas; Pryds, Ole; Netea, Mihai G; Benn, Christine Stabell; Nielsen, Susanne Dam; Jeppesen, Dorthe Lisbeth

    2017-09-29

    The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4 + T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8 + T cells), and reduced proportions of late differentiated CD4 + T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4 + T cells at 13 months (GMR = 0.55, 95% CI (0.32-0.92), p = 0.03). In conclusion, limited overall impact of neonatal BCG vaccination on lymphocyte subsets was found in healthy Danish infants within the first 13 months of life. This is in line with the limited clinical effects of BCG observed in our setting.

  10. T-cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-tailed deer

    Science.gov (United States)

    Understanding immune responses of white-tailed deer (WTD) to infection with Mycobacterium bovis provides insight into mechanisms of pathogen control and may provide clues to development of effective vaccine strategies. WTD were vaccinated with either BCG strain Pasteur or BCG Danish. Both vaccinates...

  11. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    Science.gov (United States)

    Abdallah, Abdallah M.; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunção, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur; Malas, Tareq B.; Adroub, Sabir A.; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

    2015-01-01

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains. PMID:26487098

  12. Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau: A Randomized-controlled Trial

    NARCIS (Netherlands)

    Jensen, K.J.; Larsen, N.; Biering-Sorensen, S.; Andersen, A.; Eriksen, H.B.; Monteiro, I.; Hougaard, D.; Aaby, P.; Netea, M.G.; Flanagan, K.L.; Benn, C.S.

    2015-01-01

    BACKGROUND: Bacillus Calmette-Guerin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. METHODS: Within a randomized trial in LBW infants in

  13. CH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2009-06-01

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: "each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." They further state: "each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP charges the U.S. Department of Energy (DOE) or the Waste Isolation Pilot Plant (WIPP) management and operating (M&O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21 regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these regulations are

  14. CH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2008-09-11

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: "each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the pplication." They further state: "each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP charges the U.S. Department of Energy (DOE) or the Waste Isolation Pilot Plant (WIPP) management and operating (M&O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21 regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these regulations are

  15. RH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2008-01-01

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the 'RH-TRU 72-B cask') and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' It further states: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M and O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) 71.8, 'Deliberate Misconduct.' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, 'Packaging and Transportation of Radioactive Material,' certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, 'Reporting of Defects and Noncompliance,' regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous

  16. RH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2006-01-01

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' It further states: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M and O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 Code of Federal Regulations (CFR) 1.8, 'Deliberate Misconduct.' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, 'Packaging and Transportation of Radioactive Material,' certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, 'Reporting of Defects and Noncompliance,' regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these

  17. RH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Washington TRU Solutions LLC

    2008-01-12

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the "RH-TRU 72-B cask") and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a

  18. RH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Washington TRU Solutions LLC

    2006-11-07

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to

  19. CH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2009-01-01

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' They further state: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP charges the U.S. Department of Energy (DOE) or the Waste Isolation Pilot Plant (WIPP) management and operating (M and O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) 71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21 regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these regulations

  20. Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

    2013-01-01

    '. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

  1. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

  2. Fever of unknown origin (FUO) due to miliary BCG: The diagnostic importance of morning temperature spikes and highly elevated ferritin levels.

    Science.gov (United States)

    Cunha, Burke A; Apostolopoulou, Anna; Gian, John

    Fever of unknown origin (FUO) is defined as prolonged fever of >101 °F for at least 3 weeks that remains undiagnosed after a focused inpatient or outpatient workup. One of the most elusive FUO diagnoses is miliary tuberculosis (TB) which typically has few/no localizing signs/symptoms. Since the introduction of intravesicular Bacille Calmette-Guerin (BCG) treatment for bladder carcinoma, miliary BCG has only rarely been reported as a cause of FUO. As with miliary TB, there are few/no clues to suspect miliary BCG. We present an interesting case of FUO due to miliary BCG without any localizing signs, i.e., no lung, liver or prostate involvement. The only clues to the diagnosis of this FUO due to disseminated BCG were morning temperature spikes and otherwise unexplained highly elevated ferritin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Nuclear waste package thermal performance

    International Nuclear Information System (INIS)

    Lundberg, W.

    1985-01-01

    Given the geology, the corrosion of deep geologic nuclear waste packages depends largely on the package temperature history. Factors affecting package temperature are described, and predictions of package temperatures and resulting corrosion vs time relationships are presented and discussed for candidate geologies

  4. Advances in Packaging Methods, Processes and Systems

    Directory of Open Access Journals (Sweden)

    Nitaigour Premchand Mahalik

    2014-10-01

    Full Text Available The food processing and packaging industry is becoming a multi-trillion dollar global business. The reason is that the recent increase in incomes in traditionally less economically developed countries has led to a rise in standards of living that includes a significantly higher consumption of packaged foods. As a result, food safety guidelines have been more stringent than ever. At the same time, the number of research and educational institutions—that is, the number of potential researchers and stakeholders—has increased in the recent past. This paper reviews recent developments in food processing and packaging (FPP, keeping in view the aforementioned advancements and bearing in mind that FPP is an interdisciplinary area in that materials, safety, systems, regulation, and supply chains play vital roles. In particular, the review covers processing and packaging principles, standards, interfaces, techniques, methods, and state-of-the-art technologies that are currently in use or in development. Recent advances such as smart packaging, non-destructive inspection methods, printing techniques, application of robotics and machineries, automation architecture, software systems and interfaces are reviewed.

  5. CH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2005-01-01

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: ''each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.'' They further state: ''each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SARP charges the Waste Isolation Pilot Plant (WIPP) management and operating (M and O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) 71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.

  6. Food Packaging Materials

    Science.gov (United States)

    1978-01-01

    The photos show a few of the food products packaged in Alure, a metallized plastic material developed and manufactured by St. Regis Paper Company's Flexible Packaging Division, Dallas, Texas. The material incorporates a metallized film originally developed for space applications. Among the suppliers of the film to St. Regis is King-Seeley Thermos Company, Winchester, Ma'ssachusetts. Initially used by NASA as a signal-bouncing reflective coating for the Echo 1 communications satellite, the film was developed by a company later absorbed by King-Seeley. The metallized film was also used as insulating material for components of a number of other spacecraft. St. Regis developed Alure to meet a multiple packaging material need: good eye appeal, product protection for long periods and the ability to be used successfully on a wide variety of food packaging equipment. When the cost of aluminum foil skyrocketed, packagers sought substitute metallized materials but experiments with a number of them uncovered problems; some were too expensive, some did not adequately protect the product, some were difficult for the machinery to handle. Alure offers a solution. St. Regis created Alure by sandwiching the metallized film between layers of plastics. The resulting laminated metallized material has the superior eye appeal of foil but is less expensive and more easily machined. Alure effectively blocks out light, moisture and oxygen and therefore gives the packaged food long shelf life. A major packaging firm conducted its own tests of the material and confirmed the advantages of machinability and shelf life, adding that it runs faster on machines than materials used in the past and it decreases product waste; the net effect is increased productivity.

  7. Engineering new mycobacterial vaccine design for HIV–TB pediatric vaccine vectored by lysine auxotroph of BCG

    Science.gov (United States)

    Saubi, Narcís; Gea-Mallorquí, Ester; Ferrer, Pau; Hurtado, Carmen; Sánchez-Úbeda, Sara; Eto, Yoshiki; Gatell, Josep M; Hanke, Tomáš; Joseph, Joan

    2014-01-01

    In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)–mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA2auxo. We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA2auxo vaccine strain. The BCG.HIVA2auxo vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice–compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on “double” auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth. PMID:26015961

  8. Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life: A randomized clinical trial.

    Science.gov (United States)

    Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo; Kjærgaard, Jesper; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Jensen, Aksel Karl Georg; Aaby, Peter; Olesen, Annette Wind; Jeppesen, Dorthe Lisbeth; Benn, Christine Stabell; Kofoed, Poul-Erik

    2017-12-01

    Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a T H 2 to a T H 1 response has been suggested as a possible explanation. We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Neonatal BCG had no effect on the development of RW before 13 months of age. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer.

    Science.gov (United States)

    Suriano, Francesca; Santini, Daniele; Perrone, Giuseppe; Amato, Michela; Vincenzi, Bruno; Tonini, Giuseppe; Muda, Andrea; Boggia, Sara; Buscarini, Maurizio; Pantano, Francesco

    2013-11-05

    To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy. Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann-Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method. CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively). M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.

  10. Spinal tuberculosis with severe neurological symptoms as a complication of intravesical BCG therapy for carcinoma of the bladder.

    Science.gov (United States)

    Białecki, Jerzy; Nowak-Misiak, Mirosława; Rąpała, Kazimierz; Marczyński, Wojciech; Suchodolski, Gracjan; Truszczyńska, Aleksandra

    2016-01-01

    Non-invasive bladder cancer is effectively treated with intravesical BCG therapy. The administration of the BCG vaccine is to destroy the neoplastic lesion or prevent further recurrences. The activity of the vaccine involves boosting the immune system through the stimulation of the inflammation in the bladder. Adverse reactions after this immunotherapy are rare. The aim of the study was to present complications in the form of spinal tuberculosis and serious neurological symptoms that occurred during intravesical BCG immunotherapy for carcinoma of the bladder. The manuscript also describes a method for neurosurgical spinal cord decompression of the thoracic spine. In the first patient, aged 66, after intravesical BCG therapy for bladder carcinoma, back pain and spastic paralysis of the lower limbs were observed. The MRI and CT revealed destruction of the intervertebral disc and vertebral endplates Th11-Th12. Mycobacterium tuberculosis complex bacilli were cultured from the material obtained by puncture aspiration. In the second patient, aged 35 years, during intravesical BCG immunotherapy for carcinoma of the bladder, girdle thoracic spine pain was observed. The MRI and CT of the spine showed visible lesions characteristic of tuberculosis. Immobilization in a plaster corset and implementation of antituberculous treatment resulted in quick relief of the pain and healing of the tuberculosis focus in the spine. The cases described in the work are the first documented reports in the Polish literature of spinal tuberculosis which occurred as a complication of intravesical administration of bacilli Calmette-Guérin. The diagnosis was based on the finding of BCG vaccine bacillus with molecular methods or PCR. Full antimycobacterial treatment was implemented. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Value of hilar tomography in children with positive tuberculin reaction and not inoculated with BCG

    International Nuclear Information System (INIS)

    Fritsch, R.; Mueller, H.; Hardt, H. von der

    1983-01-01

    X-ray films of the thorax in two levels were prepared of 15 children of 3-14 years of age who had not been BCG-inoculated, after the tuberculin test had shown a positive reaction. Besides bacteriology and bronchoscopy, tomography of the hilus and of the anterior mediastinum was performed to exclude hilar lymph node enlargements. In this manner, it became possible to disclose an enlargement of lymphatic nodes in four children in whom plain radiography of the thorax had not yielded any abnormal findings. (orig.) [de

  12. Food packages for Space Shuttle

    Science.gov (United States)

    Fohey, M. F.; Sauer, R. L.; Westover, J. B.; Rockafeller, E. F.

    1978-01-01

    The paper reviews food packaging techniques used in space flight missions and describes the system developed for the Space Shuttle. Attention is directed to bite-size food cubes used in Gemini, Gemini rehydratable food packages, Apollo spoon-bowl rehydratable packages, thermostabilized flex pouch for Apollo, tear-top commercial food cans used in Skylab, polyethylene beverage containers, Skylab rehydratable food package, Space Shuttle food package configuration, duck-bill septum rehydration device, and a drinking/dispensing nozzle for Space Shuttle liquids. Constraints and testing of packaging is considered, a comparison of food package materials is presented, and typical Shuttle foods and beverages are listed.

  13. ESAT-6 and HspX improve the effectiveness of BCG to induce human dendritic cells-dependent Th1 and NK cells activation.

    Directory of Open Access Journals (Sweden)

    Laura Marongiu

    Full Text Available The limited efficacy of the BCG vaccine against tuberculosis is partly due to the missing expression of immunogenic proteins. We analyzed whether the addition to BCG of ESAT-6 and HspX, two Mycobacterium tuberculosis (Mtb antigens, could enhance its capacity to activate human dendritic cells (DCs. BCG showed a weak ability to induce DC maturation, cytokine release, and CD4(+ lymphocytes and NK cells activation. The addition of ESAT-6 or HspX alone to BCG-stimulated DC did not improve these processes, whereas their simultaneous addition enhanced BCG-dependent DC maturation and cytokine release, as well as the ability of BCG-treated DCs to stimulate IFN-γ release and CD69 expression by CD4(+ lymphocytes and NK cells. Addition of TLR2-blocking antibody decreased IL-12 release by BCG-stimulated DCs incubated with ESAT-6 and HspX, as well as IFN-γ secretion by CD4(+ lymphocytes co-cultured with these cells. Moreover, HspX and ESAT-6 improved the capacity of BCG-treated DCs to induce the expression of memory phenotype marker CD45RO in naïve CD4(+ T cells. Our results indicate that ESAT-6 and HspX cooperation enables BCG-treated human DCs to induce T lymphocyte and NK cell-mediated immune responses through TLR2-dependent IL-12 secretion. Therefore ESAT-6 and HspX represent good candidates for improving the effectiveness of BCG vaccination.

  14. Adaptable imaging package for remote vehicles

    Directory of Open Access Journals (Sweden)

    Jean-Luc Liardon

    2017-10-01

    Full Text Available An easy-to-customize, low-cost solution for remote imagery is described. The system, denoted ImPROV (Imaging Package for Remote Vehicles, supports multiple cameras, live streaming, long-range encrypted communication using mobile networks, positioning and time-stamped imagery, etc. The adaptability of the system is demonstrated by its deployment on different remotely operated or autonomous vehicles, which include model aircraft, drones, balloon, kite and a submarine.

  15. CH Packaging Program Guidance

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-12-13

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: "each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." They further state: "each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP charges the U.S. Department of Energy (DOE) or the Waste Isolation Pilot Plant (WIPP) management and operating (M&O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21 regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these regulations are

  16. CH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2006-01-01

    The purpose of this document is to provide the technical requirements for preparation for use, operation, inspection, and maintenance of a Transuranic Package Transporter Model II (TRUPACT-II), a HalfPACT shipping package, and directly related components. This document complies with the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP), HalfPACT SARP, and U.S. Nuclear Regulatory Commission (NRC) Certificates of Compliance (C of C) 9218 and 9279, respectively. In the event of a conflict between this document and the SARP or C of C, the C of C shall govern. The C of Cs state: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' They further state: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP charges the U.S. Department of Energy (DOE) or the Waste Isolation Pilot Plant| (WIPP) management and operating (M and O) contractor with assuring packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations(CFR) 71.8. Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21 regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these regulations

  17. Preparation of a working seed lot of BCG and quality control by PCR genotyping Preparación de un lote semilla de trabajo de BCG y control de calidad por genotipificación por PCR

    Directory of Open Access Journals (Sweden)

    A Trovero

    2010-02-01

    Full Text Available The bacillus Calmette-Guérin (BCG was obtained in 1920 after successive passages leading to the attenuation of a Mycobacterium bovis strain. For the following 40 years, BCG had been replicated, resulting in substrains with genotypic and phenotypic differences. Several genomic studies have compared two BCG strains, M. bovis and Mycobacterium tuberculosis, and observed that deleted regions in the different strains could be related to differences in antigenic properties. In this work, a working seed lot was obtained from a lyophilized secondary seed lot from the BCG Pasteur strain 1173 P2 and genetically characterized. The genome was analyzed by PCR directed to five regions (RD1, RD2, RD14, RD15, DU2, using the seed lot and different available strains as templates. No genetic differences were found in the fragments studied as compared to the Pasteur strain. A total of 20 passages were carried out and no differences were found in the size of the fragments amplified by PCR. In conclusion, this method allows to control a working seed lot genotypically and to assess the stability of the BCG genome.El bacilo de Calmette-Guérin (BCG se obtuvo en 1920, después de sucesivos pasajes que llevaron a la atenuación de una cepa de Mycobacterium bovis. A lo largo de los 40 años subsiguientes la cepa BCG fue replicada y surgieron subcepas con diferencias fenotípicas y genotípicas. Se realizaron varios estudios de comparación genómica de diferentes cepas de BCG, M. bovis y Mycobacterium tuberculosis, y se observó que las deleciones de regiones en las diferentes cepas podrían estar relacionadas con diferencias en las propiedades antigénicas. En este trabajo se describe la preparación y caracterización genética de un lote semilla de trabajo obtenido a partir de un lote semilla secundaria liofilizado de la cepa BCG Pasteur 1173 P2. Se analizaron por PCR cinco regiones (RD1, RD2, RD14, RD15, DU2 en el lote semilla de trabajo utilizando como control las

  18. Antigen-specific CD4 T cells are induced after intravesical BCG-instillation therapy in patients with bladder cancer and show similar cytokine profiles as in active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Julia Elsäßer

    Full Text Available Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette-Guérin (BCG in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN-γ and interleukin (IL-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007. Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003. Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02, whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01. In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG

  19. Waste package characterisation

    International Nuclear Information System (INIS)

    Sannen, L.; Bruggeman, M.; Wannijn, J.P.

    1998-09-01

    Radioactive wastes originating from the hot labs of the Belgian Nuclear Research Centre SCK-CEN contain a wide variety of radiotoxic substances. The accurate characterisation of the short- and long-term radiotoxic components is extremely difficult but required in view of geological disposal. This paper describes the methodology which was developed and adopted to characterise the high- and medium-level waste packages at the SCK-CEN hot laboratories. The proposed method is based on the estimation of the fuel inventory evacuated in a particular waste package; a calculation of the relative fission product contribution on the fuel fabrication and irradiation footing; a comparison of the calculated, as expected, dose rate and the real measured dose rate of the waste package. To cope with the daily practice an appropriate fuel inventory estimation route, a user friendly computer programme for fission product and corresponding dose rate calculation, and a simple dose rate measurement method have been developed and implemented

  20. Waste package characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Sannen, L.; Bruggeman, M.; Wannijn, J.P

    1998-09-01

    Radioactive wastes originating from the hot labs of the Belgian Nuclear Research Centre SCK-CEN contain a wide variety of radiotoxic substances. The accurate characterisation of the short- and long-term radiotoxic components is extremely difficult but required in view of geological disposal. This paper describes the methodology which was developed and adopted to characterise the high- and medium-level waste packages at the SCK-CEN hot laboratories. The proposed method is based on the estimation of the fuel inventory evacuated in a particular waste package; a calculation of the relative fission product contribution on the fuel fabrication and irradiation footing; a comparison of the calculated, as expected, dose rate and the real measured dose rate of the waste package. To cope with the daily practice an appropriate fuel inventory estimation route, a user friendly computer programme for fission product and corresponding dose rate calculation, and a simple dose rate measurement method have been developed and implemented.

  1. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2009-01-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  2. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2014-07-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  3. gap: Genetic Analysis Package

    Directory of Open Access Journals (Sweden)

    Jing Hua Zhao

    2007-06-01

    Full Text Available A preliminary attempt at collecting tools and utilities for genetic data as an R package called gap is described. Genomewide association is then described as a specific example, linking the work of Risch and Merikangas (1996, Long and Langley (1997 for family-based and population-based studies, and the counterpart for case-cohort design established by Cai and Zeng (2004. Analysis of staged design as outlined by Skol et al. (2006 and associate methods are discussed. The package is flexible, customizable, and should prove useful to researchers especially in its application to genomewide association studies.

  4. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N Peter; Steineck, Gunnar; Schumacher, Martin C; de Verdier, Petra J

    2015-12-01

    Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Our results suggest that the investigated polymorphisms influence patient response

  5. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes.

    Directory of Open Access Journals (Sweden)

    Guillaume Tabouret

    2010-10-01

    Full Text Available The species-specific phenolic glycolipid 1 (PGL-1 is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3 for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells.

  6. The humoral immune response after BCG vaccination in humans: consequences for the serodiagnosis of tuberculosis.

    Science.gov (United States)

    Turneer, M; Van Vooren, J P; Nyabenda, J; Legros, F; Lecomte, A; Thiriaux, J; Serruys, E; Yernault, J C

    1988-07-01

    The IgM and IgG response to BCG vaccination was investigated in 75 adults, tuberculin negative before vaccination, using an enzyme-linked immunosorbent assay with purified protein derivative (PPD) as antigen. The mean optical density (OD) increased significantly (p less than 0.001) in both immunoglobulin classes. Increase in at least one class was significant in 89% of the subjects. The observed increase in anti-PPD IgG was rather small but comparable to that seen in 17 newly diagnosed tuberculosis patients with negative direct smear [mean OD (SD): 0.59 (0.38) in vaccinated and 0.70 (0.48) in patients] but significantly lower (p less than 0.001) than that seen in 31 newly diagnosed patients with positive direct smear [mean OD (SD): 1.07 (0.67)]. With 55% of sera above the upper normal limit, smear positive patients differentiated (p less than 0.001) from vaccinated subjects (20% of positive sera) whilst smear negative patients (29% of positive sera) did not. We conclude that BCG vaccination induces a definite but small increase in anti-PPD serum IgM and IgG, which is likely to interfere when interpreting serological tests for the diagnosis of tuberculosis, especially in those patients who would most benefit from an early and fast diagnosis.

  7. Complications after BCG vaccination in a big city

    Directory of Open Access Journals (Sweden)

    T. A. Sevostyanova

    2016-01-01

    Full Text Available Complications after specific prevention of tuberculosis for the last 10 years have been analyzed using the example of a big city. The frequency of severe complications (BCG-ostitis made 0.004% and the frequency of minor complications (lymphadenitis made 0.005% and cold abscesses made 0.01% per 100 000 vaccinated children. Often complications were caused by mistakes in the vaccine administration related to premature discharge from maternity hospital and administration of the vaccine in the polyclinic and also concurrent prenatal disorder. The issue of complications caused by anti-tuberculosis vaccination makes no grounds to review the policy of the primary BCG vaccination.

  8. An evaluation of a supplementary road safety package.

    Science.gov (United States)

    Guria, Jagadish; Leung, Joanne

    2004-09-01

    A Supplementary Road Safety Package (SRSP) was developed in New Zealand in 1995/1996 to supplement the compulsory breath test (CBT) and speed camera programmes introduced in 1993. A major feature of the package was the use of emotion and shock advertising campaigns not only to affect high risk driving attitudes and behaviours towards speeding and drink-driving but also to encourage the use of safety belts. Furthermore, the SRSP also emphasised targeting enforcement to these three areas. This package continued for 5 years. This paper estimates the effect of the package on road trauma. The analysis shows that the Package made substantial impact on road safety and saved over 285 lives over the 5-year period. Copyright 2003 Elsevier Ltd.

  9. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

    Directory of Open Access Journals (Sweden)

    Niels Brimnes

    2011-02-01

    Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

  10. Síndrome de reconstitución inmune por BCG en niños tratados por VIH Immune reconstitution syndrome due to BCG in HIV-treated children

    Directory of Open Access Journals (Sweden)

    Edwin Miranda-Choque

    2012-12-01

    Full Text Available El objetivo del estudio fue describir el perfil clínico del síndrome de reconstitución inmune por Mycobacterium bovis Bacillus Calmette-Guérin (SIRI-BCG en niños con infección VIH que reciben tratamiento antirretroviral de gran actividad (TARGA en el Instituto Nacional de Salud del Niño de Lima, Perú. Se realizó un estudio de serie de casos, que incluyó ocho niños con SIRI-BCG, definido como la presencia de linfadenopatía regional o inflamación en sitio de inoculación de BCG con disminución de al menos un logaritmo en la carga viral o mejoría inmunológica. Todos los pacientes tenían estadio SIDA (C3. La mediana de edad de inicio del TARGA fue de 7,2 meses y el evento se produjo entre 3 a 11 semanas luego de haberlo iniciado. En siete casos se produjo adenitis axilar. Al comparar con el grupo sin SIRI-BCG se encontró asociación significativa con la edad de inicio del TARGA de un año, estado de inmunodepresión severa, y carga viral incrementada. Se concluye que el SIRI-BCG está relacionado con una rápida progresión clínica de la infección VIH/SIDA de trasmisión vertical, estadio de inmunosupresión severa, y carga viral alta al momento del inicio del TARGA.The objective of this study is to describe the clinical profile of the immune reconstitution syndrome due to Mycobacterium bovis Bacillus Calmette-Guérin (IRS-BCG in children with HIV infection who receive highly active antiretroviral treatment (HAART at Instituto Nacional de Salud del Niño de Lima (National Children’s Health Institute of Lima, Peru. A case study was conducted, including 8 children with IRS-BCG, defined as the presence of regional lymphadenopathy or inflammation on the BCG vaccination site with at least one less logarithm in the viral load or immune improvement. All patients had AIDS (C3. The starting median age in HAART was 7.2 months and the event occurred 3 to 11 weeks after the treatment was started. 7 cases showed axillary adenitis. When

  11. Prova tuberculínica, BCG oral e infecção tuberculosa em crianças menores de 5 anos Tuberculin test, oral BCG vaccine, and tuberculosis infection among children under five years of age

    Directory of Open Access Journals (Sweden)

    Marialda Höfling de Pádua Dias

    1978-12-01

    Full Text Available São relatados os resultados das provas tuberculínicas com PPD Rt23, 2 UT, em crianças menores de um ano e de um a 4 anos, matriculadas na Clínica Pediátrica do Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brasil, no período de 1971 a 1975. Em 665 crianças menores de um ano encontrou-se 3,15% de reatores fracos e 6,62% de reatores fortes e em 1.298 crianças de um a 4 anos, 0,69% de reatores fracos e 5,5% de reatores fortes. Nas mesmas crianças, foram estudadas as relações entre vacinação BCG oral prévia e positividade à prova tuberculínica nos 2 grupos etários considerados e nos quais se obteve a informação de vacinação anterior com BCG oral. Em 575 crianças menores de um ano e 1.113 de um a 4 anos encontrou-se associação positiva entre vacinação BCG oral prévia e positividade à prova tuberculínica. Analisando a relação entre o número de doses de BCG oral prévio e o resultado das provas tuberculínicas pelo método de Goodman, verificou-se que a proporção de crianças que tinham tomado 3 doses e mais de BCG oral e que apresentaram reação forte à prova tuberculínica é significantemente maior que a observada para os não reatores, fato esse não verificado para o grupo de um a 4 anos. Nas crianças que tomaram uma ou duas doses não foram encontradas diferenças estatisticamente significantes.Results of tuberculin reaction from PPD Rt 23, 2UT are reported on children under one year of age and children from one to four years of age who were registered in the Pediatric Clinics of the Hospital das Clinicas of the College of Medicine of the State University of São Paulo. The study was carried out from 1971 through 1975. In a group of 665 children under one year of age, 3.15% were weak reactors while 6.62% were strong reactors, and, in a group of 1298 children between one to four years of age, 0.69% were weak reactors while 5.5% were strong reactors. The relationship between prior BCG oral

  12. Electro-Microfluidic Packaging

    Science.gov (United States)

    Benavides, G. L.; Galambos, P. C.

    2002-06-01

    There are many examples of electro-microfluidic products that require cost effective packaging solutions. Industry has responded to a demand for products such as drop ejectors, chemical sensors, and biological sensors. Drop ejectors have consumer applications such as ink jet printing and scientific applications such as patterning self-assembled monolayers or ejecting picoliters of expensive analytes/reagents for chemical analysis. Drop ejectors can be used to perform chemical analysis, combinatorial chemistry, drug manufacture, drug discovery, drug delivery, and DNA sequencing. Chemical and biological micro-sensors can sniff the ambient environment for traces of dangerous materials such as explosives, toxins, or pathogens. Other biological sensors can be used to improve world health by providing timely diagnostics and applying corrective measures to the human body. Electro-microfluidic packaging can easily represent over fifty percent of the product cost and, as with Integrated Circuits (IC), the industry should evolve to standard packaging solutions. Standard packaging schemes will minimize cost and bring products to market sooner.

  13. YWCA Vocational Readiness Package.

    Science.gov (United States)

    Scott, Jeanne

    This document outlines, in detail, the Vocational Readiness Package for young girls, which is a week-long program utilizing simulation games and role-playing, while employing peer group counseling techniques to dramatize the realities concerning women in marriage and careers today. After three years of using this program, the authors have compiled…

  14. Waste disposal package

    Science.gov (United States)

    Smith, M.J.

    1985-06-19

    This is a claim for a waste disposal package including an inner or primary canister for containing hazardous and/or radioactive wastes. The primary canister is encapsulated by an outer or secondary barrier formed of a porous ceramic material to control ingress of water to the canister and the release rate of wastes upon breach on the canister. 4 figs.

  15. Aquaculture Information Package

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, T.; Rafferty, K. [editors

    1998-01-01

    This package of information is intended to provide background to developers of geothermal aquaculture projects. The material is divided into eight sections and includes information on market and price information for typical species, aquaculture water quality issues, typical species culture information, pond heat loss calculations, an aquaculture glossary, regional and university aquaculture offices and state aquaculture permit requirements.

  16. Packaging LLW and ILW

    International Nuclear Information System (INIS)

    Flowers, R.H.; Owen, R.G.

    1991-01-01

    Low level waste (LLW) accounts for 70-80% by volume of all radioactive wastes produced by the nuclear industry. It has low specific activity, negligible actinide content and requires little, if any, shielding to protect workers. Volume reduction for LLW of high volume but low density may be achieved by incineration and compaction as appropriate, before packaging for disposal by near surface burial. Intermediate level waste (ILW) is treated and packed to convert it into a stable form to minimize any release of activity and make handling easier. The matrix chosen for immobilization, usually cement, polymers or bitumen, depends on the nature of the waste and the acceptance criteria of the disposal facility. The special case of LLW and ILW which will arise from reactor decommissioning is discussed. Packaging methods adopted by individual countries are reviewed. The range of costs involved for packaging ILW is indicated. There is no international consensus on the performance required from packaged waste to ensure its suitability both for interim storage and final disposal. (UK)

  17. Openability of tamperproof packaging

    NARCIS (Netherlands)

    Del Castillo C., A.; Wever, R.; Buijs, P.J.; Stevels, A.

    2007-01-01

    Communication, product protection and presentation are three key aspects in the world of packaging nowadays. Due to a retail landscape consisting of large stores, displaying packed products on the shelves in self-service environments, these aspects become increasingly important, not only for Fast

  18. CH Packaging Maintenance Manual

    International Nuclear Information System (INIS)

    Washington TRU Solutions

    2002-01-01

    This procedure provides instructions for performing inner containment vessel (ICV) and outer containment vessel (OCV) maintenance and periodic leakage rate testing on the following packaging seals and corresponding seal surfaces using a nondestructive helium (He) leak test. In addition, this procedure provides instructions for performing ICV and OCV structural pressure tests

  19. Printer Graphics Package

    Science.gov (United States)

    Blanchard, D. C.

    1986-01-01

    Printer Graphics Package (PGP) is tool for making two-dimensional symbolic plots on line printer. PGP created to support development of Heads-Up Display (HUD) simulation. Standard symbols defined with HUD in mind. Available symbols include circle, triangle, quadrangle, window, line, numbers, and text. Additional symbols easily added or built up from available symbols.

  20. Geothermal Greenhouse Information Package

    Energy Technology Data Exchange (ETDEWEB)

    Rafferty, K. [P.E.; Boyd, T. [ed.

    1997-01-01

    This package of information is intended to provide a foundation of background information for developers of geothermal greenhouses. The material is divided into seven sections covering such issues as crop culture and prices, operating costs for greenhouses, heating system design, vendors and a list of other sources of information.

  1. Vaccination with Mycobacterium bovis BCG strains Danish and Pasteur in white-tailed deer (Odocoileus virginianus) experimentally challenged with Mycobacterium bovis.

    Science.gov (United States)

    Palmer, M V; Thacker, T C; Waters, W R

    2009-06-01

    Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis in domestic livestock and the cause for many faltering bovine tuberculosis eradication programmes. One approach in dealing with wildlife reservoirs of disease is to interrupt inter-species and intraspecies transmission through vaccination of deer or cattle. To evaluate the efficacy of BCG vaccination in white-tailed deer, 35 deer were assigned to one of three groups; one s.c. dose of 10(7) CFU of M. bovis BCG Pasteur (n = 12); 1 s.c. dose of 10(7) CFU of M. bovis BCG Danish (n = 11); or unvaccinated deer (n = 12). After vaccination, deer were inoculated intratonsilarly with virulent M. bovis. Lesion severity scores of the medial retropharyngeal lymph node, as well as all lymph nodes combined, were reduced in vaccinated deer compared to unvaccinated deer. BCG Danish vaccinated deer had no late stage granulomas characterized by coalescent caseonecrotic granulomas containing numerous acid-fast bacilli compared to BCG Pasteur vaccinated or unvaccinated deer where such lesions were present. Both BCG strains were isolated as late as 250 days after vaccination from deer that were vaccinated but not challenged. In white-tailed deer, BCG provides protection against challenge with virulent M. bovis. Issues related to vaccine persistence, safety and shedding remain to be further investigated.

  2. Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

    Science.gov (United States)

    Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

    2017-06-01

    Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

  3. A Mycobacterium bovis BCG-Naked DNA Prime-Boost Vaccination Strategy Induced CD4+ and CD8+ T-Cell Response against Mycobacterium tuberculosis Immunogens

    Directory of Open Access Journals (Sweden)

    Miao Lu

    2014-01-01

    Full Text Available Mycobacterium tuberculosis infection is still a major global public health problem. Presently the only tuberculosis (TB vaccine available is Bacille Calmette-Guérin (BCG, although it fails to adequately protect against pulmonary TB in adults. To solve this problem, the development of a new effective vaccine is urgently desired. BCG-prime DNA-booster vaccinations strategy has been shown to induce greater protection against tuberculosis (TB than BCG alone. Some studies have demonstrated that the two genes (Rv1769 and Rv1772 are excellent T-cell antigens and could induce T-cell immune responses. In this research, we built BCG-C or BCG-P prime-recombination plasmid PcDNA3.1-Rv1769 or PcDNA3.1-Rv1772 boost vaccinations strategy to immunize BALB/c mice and evaluated its immunogenicity. The data suggests that the BCG-C+3.1-72 strategy could elicit the most long-lasting and strongest Th1-type cellular immune responses and the BCG-C+3.1-69 strategy could induce the high level CD8+ T-cell response at certain time points. These findings support the ideas that the prime-boost strategy as a combination of vaccines may be better than a single vaccine for protection against tuberculosis.

  4. Technology transfer package on seismic base isolation - Volume III

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-02-14

    This Technology Transfer Package provides some detailed information for the U.S. Department of Energy (DOE) and its contractors about seismic base isolation. Intended users of this three-volume package are DOE Design and Safety Engineers as well as DOE Facility Managers who are responsible for reducing the effects of natural phenomena hazards (NPH), specifically earthquakes, on their facilities. The package was developed as part of DOE's efforts to study and implement techniques for protecting lives and property from the effects of natural phenomena and to support the International Decade for Natural Disaster Reduction. Volume III contains supporting materials not included in Volumes I and II.

  5. Histiocytic lymphoma in the brain as the only manifestation of relapse following remission maintainance with BCG immunotherapy.

    Science.gov (United States)

    Snyder, R D; Mavligit, G M; Valdivieso, M; Gutterman, J U; Burke, J S

    1977-05-01

    This report describes an unusual case of lymphoma which, after 54 months of complete remission induced with chemotherapy and maintained with BCG immunotherapy, relapsed in the brain alone. It is possible that the immunotherapy led to this pattern of relapse: this is supported by several other studies. The difficulty in diagnosing brain lymphoma is emphasized.

  6. Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Nankabirwa, V.; Tumwine, J.K.; Namugga, O.; Tylleskar, T.; Ndeezi, G.; Robberstad, B.; Netea, M.G.; Sommerfelt, H.

    2017-01-01

    BACKGROUND: Bacillus Calmette-Guerin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is

  7. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

    Science.gov (United States)

    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  8. Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam

    2008-01-01

    OBJECTIVE: To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. DESIGN: Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering app...

  9. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

    2017-01-01

    and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. CONCLUSIONS AND RELEVANCE: Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero...

  10. Developing the Biological Condition Gradient (BCG), as a Tool for Describing the Condition of US Coral Reefs

    Science.gov (United States)

    Understanding effects of human activity on coral reefs requires knowing what characteristics constitute a high quality coral reef and identifying measurable criteria. The BCG is a conceptual model that describes how biological attributes of coral reefs change along a gradient of ...

  11. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

  12. Hazardous materials package performance regulations

    International Nuclear Information System (INIS)

    Russell, N.A.; Glass, R.E.; McClure, J.D.; Finley, N.C.

    1992-01-01

    The hazardous materials (hazmat) packaging development and certification process is currently defined by two different regulatory philosophies, one based on specification packagings and the other based on performance standards. With specification packagings, a packaging is constructed according to an agreed set of design specifications. In contrast, performance standards do not specify the packaging design; they specify performance standards that a packaging design must be able to pass before it can be certified for transport. The packaging can be designed according to individual needs as long as it meets these performance standards. Performance standards have been used nationally and internationally for about 40 years to certify radioactive materials (RAM) packagings. It is reasonable to state that for RAM transport, performance specifications have maintained transport safety. A committee of United Nation's experts recommended the performance standard philosophy as the preferred regulation method for hazmat packaging. Performance standards for hazmat packagings smaller than 118 gallons have been adopted in 49CFR178. Packagings for materials that are classified as toxic-by-inhalation must comply with the performance standards by October 1, 1993, and packagings for all other classes of hazardous materials covered must comply by October 1, 1996. For packages containing bulk (in excess of 188 gallons) quantities of materials that are extremely toxic by inhalation, there currently are no performance requirements. This paper discusses a Hazmat Packaging Performance Evaluation (HPPE) project to look at the subset of bulk packagings that are larger than 2000 gallons. The objectives of this project are the evaluate current hazmat specification packagings and develop supporting documentation for determining performance requirements for packagings in excess of 2000 gallons that transport hazardous materials that have been classified as extremely toxic by inhalation (METBI)

  13. Histopathological, immunohistochemical and ultraestructural evaluation of inflammatory response in Arius genus fish under experimental inoculation of BCG

    Directory of Open Access Journals (Sweden)

    Ricardo Yuji Sado

    2008-10-01

    Full Text Available The aim of this study was to evaluate the inflammatory response kinetics after experimental inoculation with BCG in the primitive Arius sp. fish. The BCG was applied through the intramuscular injection in the caudal peduncular region, and the samples were collected for the analyses at days 1, 3, 7, 14, 21, and 33 post-injection. Acute phase inflammatory infiltrate was characterized by the predominant mononuclear cells, intersticial edema, and muscular tissue necrosis. As the inflammatory response evolved, a large number of multinuclear giant cells were formed containing the BCG. These giant cells were positive for the S100 protein at the histochemical analysis, which demonstrate the macrofage activity, confirmed by the ultra-structural analysis showing the lack of the cytoplasmic membrane enveloping the many nuclei within the giant cell. These results led to the conclusion that Arius sp. fish injected with the BCG showed a difuse inflammatory response characterized by a large number of mononuclear cells, absence of granuloma formation, and predominant giant cells.Avaliou-se a cinética da resposta inflamatória induzida experimentalmente com BCG em peixes primitivos pertencentes ao gênero Arius. Os animais foram inoculados com BCG por via intramuscular na região do pedúnculo caudal, sendo realizada a coleta do material nos tempos experimentais de 1, 3, 7, 14, 21 e 33 dias pós-inoculação. A fase aguda da resposta inflamatória se mostrou na forma de infiltrado inflamatório composto predominantemente por células mononucleares, edema intersticial e necrose de tecido muscular. À medida que o processo se desenvolveu, houve formação e aumento no número de células gigantes multinucleadas envolvendo o inóculo. Essas células gigantes, ao exame imunohistoquímico, apresentaram positividade à proteína S100 indicando ação de células macrofágicas, além da ultraestrutura apontar a ausência de membrana citoplasmática entre os in

  14. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of a randomized controlled trial.

    Science.gov (United States)

    Kiraly, N; Benn, C S; Biering-Sørensen, S; Rodrigues, A; Jensen, K J; Ravn, H; Allen, K J; Aaby, P

    2013-09-01

    Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96). There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. Clinicaltrials.gov NCT 01420705. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection.

    Science.gov (United States)

    Seddon, James A; Paton, James; Nademi, Zohreh; Keane, Denis; Williams, Bhanu; Williams, Amanda; Welch, Steven B; Liebeschutz, Sue; Riddell, Anna; Bernatoniene, Jolanta; Patel, Sanjay; Martinez-Alier, Nuria; McMaster, Paddy; Kampmann, Beate

    2016-10-01

    Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity. Children vaccination on TST positivity was evaluated in IGRA-negative children, as was the performance of different TST cut-offs to predict IGRA positivity. Of 422 children recruited (median age 69 months; IQR: 32-113 months), 300 (71%) had been vaccinated with BCG. BCG vaccination affected the TST response in IGRA-negative children less than 5 years old but not in older children. A 5 mm TST cut-off demonstrated good sensitivity and specificity in BCG-unvaccinated children, and an excellent negative predictive value but was associated with low specificity (62.7%; 95% CI 56.1% to 69.0%) in BCG-vaccinated children. For BCG-vaccinated children, a 10 mm cut-off provided a high negative predictive value (97.7%; 95% CI 94.2% to 99.4%) with the positive predictive value increasing with increasing age of the child. BCG vaccination had little impact on TST size in children over 5 years of age. The revised TST cut-off recommended in the recent revision to the UK TB guidelines demonstrates good sensitivity but is associated with impaired specificity in BCG-vaccinated children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

    Science.gov (United States)

    Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

    2013-10-05

    Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

  17. In-Package Chemistry Abstraction

    Energy Technology Data Exchange (ETDEWEB)

    P.S. Domski

    2003-07-21

    The work associated with the development of this model report was performed in accordance with the requirements established in ''Technical Work Plan for Waste Form Degradation Modeling, Testing, and Analyses in Support of SR and LA'' (BSC 2002a). The in-package chemistry model and in-package chemistry model abstraction are developed to predict the bulk chemistry inside of a failed waste pac