WorldWideScience

Sample records for bcg vaccine

  1. BCG vaccine in Korea

    OpenAIRE

    Joung, Sun Myung; Ryoo, Sungweon

    2013-01-01

    The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and ...

  2. 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. ...

  3. Tuberculous Meningitis in BCG-Vaccinated Children

    Directory of Open Access Journals (Sweden)

    M Movahhedi

    1998-05-01

    Full Text Available It is generally accepted that BCG vaccination is fully effective in preventing Tuberculous Meningitis and military Tuberculous, although it does not develop complete immunity for Tuberculous infection of lungs and other organs. A series of 3 children with Tuberculous Meningitis who had positive history of BCG vaccination as newborns and distinct BCG scar show that Tuberculous Meningitis may be caught despite successful BCG vaccination.

  4. 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.

  5. Nonclinical Development of BCG Replacement Vaccine Candidates

    OpenAIRE

    Bernd Eisele; Martin Gengenbacher; Reginald Kidd; David McCown; Sheldon Morris; Steven Derrick; David Hokey; Dominick Laddy; Rosemary Chang; Megan Fitzpatrick; Leander Grode; Kamalakannan Velmurugan; Stefan H. E. Kaufmann; John Fulkerson; Brennan, Michael J.

    2013-01-01

    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 ...

  6. Tuberculous spondylitis following BCG vaccination

    International Nuclear Information System (INIS)

    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.)

  7. Polyneuritis following BCG re-vaccination

    OpenAIRE

    Katznelson, D; Gross, S.; Sack, J

    1982-01-01

    A 12-year-old healthy, tuberculin negative boy was re-vaccinated with BCG. Nine days later symmetrical polyneuritis developed in all extremities. The tuberculin test was now strongly positive. It is suggested that the polyneuritis was due to a hypersensitivity reaction resulting from the BCG re-vaccination.

  8. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-01-01

    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. PMID:26343962

  9. 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.

  10. Susceptibility of Mycobacterium bovis BCG Vaccine Strains to Antituberculous Antibiotics▿

    OpenAIRE

    Ritz, Nicole; Tebruegge, Marc; Connell, Tom G.; Sievers, Aina; Robins-Browne, Roy; Curtis, Nigel

    2008-01-01

    Mycobacterium bovis BCG is one of the most commonly administered vaccines. Complications, including disseminated BCG disease, are rare but increasingly reported in immunodeficient children. There is growing recognition of the importance of differences between BCG vaccine strains. We determined the susceptibilities of five genetically distinct BCG vaccine strains to 12 antituberculous drugs.

  11. Osteíte por BCG Osteitis after BCG vaccination

    Directory of Open Access Journals (Sweden)

    André Fukunishi Yamada

    2009-03-01

    Full Text Available Os autores relatam o caso de um menino de 1 ano e 9 meses que apresentou lesão osteolítica na região proximal do úmero direito. Com base na história clínica e em achados histológicos, os autores suspeitaram de osteíte pósvacina BCG. Após o início do tratamento antituberculose, os sintomas desapareceram e o paciente apresentou melhora radiológica. Os autores descrevem esta entidade incomum na prática pediátrica e alertam para possíveis complicações da vacina BCG.The authors report the case of a 21-month-old boy with an osteolytic lesion in the proximal region of the right humerus. Based on the clinical history and histological findings, the authors suspected osteitis following BCG vaccination. Symptoms remitted after antituberculosis therapy was initiated, and the patient presented radiological improvement. The authors describe this uncommon entity in pediatric practice and call attention to possible complications of BCG vaccination.

  12. Evaluation of BCG Vaccine in Excessive Dermal Reactivity Test

    OpenAIRE

    Malik, Neeraj; Kasana, Harit; Sikarwar, Gunjan; Pathania, Lavanyam; Tewari, Shalini; Kiran, Manjula; Soni, G. R.; Singh, Surinder

    2015-01-01

    BCG vaccine has been in use globally to control the tuberculosis since the year 1921 and there has been significant achievement to curtail the disease. The important tests as per pharmacopoeial requirements including count of viable units (CVU) and excessive dermal reactivity (EDR) are required to be performed for ensuring the quality of BCG vaccine. In order to see the trend analysis of EDR of BCG vaccine used in India, a study has been carried out using 35 batches of BCG vaccine manufacture...

  13. 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.

  14. 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.

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

    DEFF Research Database (Denmark)

    Thysen, Sanne Marie; Byberg, Stine; Pedersen, Marie; Rodrigues, Amabelia; Ravn, Henrik; Martins, Cesario; Benn, Christine Stabell; Aaby, Peter; Fisker, Ane Bærent

    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...... visits 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...

  16. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices

    OpenAIRE

    2011-01-01

    Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user friendly Web site for TB clinicians to discern global BCG vaccination policies and practices and improve the care of their patients.

  17. Doit-on encore recommander le vaccin BCG?

    OpenAIRE

    Collette, Georges; Bourhaba, Maryam; Moutschen, Michel

    2006-01-01

    The BCG vaccine has demonstrated its efficacy to protect young children from severe extrapulmonary forms of tuberculosis. Nevertheless, the immunity induced by the vaccine disappears in adults and cannot be boosted by readministration of BCG. Adverse effects of BCG are rare, but potentially dangerous (i.e. disseminated vaccinal infections) and they justify the fact that BCG should not be administered anymore in Western European countries where the incidence of pediatric tuberculous meningitis...

  18. Safety and Immunogenicity of Boosting BCG Vaccinated Subjects with BCG: Comparison with Boosting with a New TB Vaccine, MVA85A

    OpenAIRE

    Whelan, KT; Pathan, AA; Sander, CR; Fletcher, HA; Poulton, I; Alder, NC; Hill, AV; Mcshane, H.

    2009-01-01

    OBJECTIVES To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses ...

  19. Tuberculin reactivity of children vaccinated at different age with BCG vaccines in preschool period

    OpenAIRE

    Sučilienė, Elena

    2010-01-01

    Object of dissertation: The influence of different BCG vaccination schedules on the tuberculin reactivity, BCG scarring, specific serology and allergy. 509 children were included in this research, all of them received BCG vaccination with standard or half dosage as newborns or 3-months old. 3 months after BCG vaccination and at one, two, and six years of age they were tested with tuberculin, and examined for BCG scarring. Anti-tuberculosis antibodies were detected in sera and children were ev...

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. Genome sequencing and analysis of BCG vaccine strains.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available BACKGROUND: Although the Bacillus Calmette-Guérin (BCG vaccine against tuberculosis (TB has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. METHODS AND FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359, lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908-1966. CONCLUSIONS: Our results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

  3. 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

  4. Tuberculin skin reactivity four years after neonatal BCG vaccination.

    OpenAIRE

    Ormerod, L P; Garnett, J M

    1992-01-01

    Two hundred and sixty one of 279 (93.5%) children known to be tuberculin positive shortly after receiving their neonatal BCG vaccination were still tuberculin positive at age 4 years. The results confirm the continuing effectiveness of neonatal BCG at 4 years.

  5. Manipulation of BCG vaccine: a double-edged sword.

    Science.gov (United States)

    Singh, V K; Srivastava, R; Srivastava, B S

    2016-04-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach. PMID:26810060

  6. Genome Sequencing and Analysis of BCG Vaccine Strains

    OpenAIRE

    Zhang, Wen; Zhang, Yuanyuan; Zheng, Huajun; Pan, Yuanlong; Liu, Haican; Du, Pengcheng; Wan, Li; LIU Jun; Zhu, Baoli; Zhao, Guoping; Chen, Chen; Wan, Kanglin

    2013-01-01

    Background Although the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. Methods and Findings Comparative genomic analysis of 1...

  7. Disseminated tuberculoid lesions in infants following BCG vaccination.

    OpenAIRE

    Trevenen, C. L.; Pagtakhan, R. D.

    1982-01-01

    The records of 830 consecutive autopsies at Children's Hospital, Winnipeg revealed that 26 of the 36 infants (34 Canadian Indian, 1 Inuit and 1 Caucasian) given BCG vaccine shortly after birth had tuberculoid granulomas in various sites, including the vaccination site, regional lymph nodes, liver, spleen, lung, bone marrow and salivary gland. Mycobacterium bovis, BCG type, was identified in three of the four cases in which isolation was attempted. The principal causes of death had been sudden...

  8. 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.

  9. 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.; van de Sande, P.J.M.; Whittle, H.; Fisker, Bent; Roth, A.; Aaby, Peter; Yazdanbakhsh, M.; Benn, Christine Stabell

    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...... 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...... 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...

  10. Recombinant Mycobacterium bovis BCG as an HIV Vaccine Vector

    OpenAIRE

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-01-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addi...

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

    International Nuclear Information System (INIS)

    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.

  12. Recombinant Mycobacterium bovis BCG as an HIV vaccine vector.

    Science.gov (United States)

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-06-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID:20353397

  13. 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.

  14. 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.

  15. The Current Status of BCG Vaccination in Young Children in South Korea

    OpenAIRE

    Lee, Hyejon; Dockrell, Hazel M.; Kim, Deok Ryun; FLOYD, Sian; Oh, Sue Yeon; Lee, Jin Bum; Kim, Hee Jin

    2012-01-01

    Background Delivery of Bacille Calmette-Guréin (BCG) Tokyo vaccine, with the multipuncture device, has been much preferred over BCG Pasteur, with the intradermal method, possibly due to the easier manner of administration, a desire to avoid any trouble with scars, as well as side effects and higher profits to providers in South Korea. Methods To determine BCG scar status in 0~6 year old children vaccinated with two BCG vaccines (Pasteur BCG vaccine with intradermal method and BCG Tokyo vaccin...

  16. Trained immunity: consequences for the heterologous effects of BCG vaccination

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; Crevel, R. van; Netea, M.G.

    2015-01-01

    A growing body of evidence from epidemiologic and immunologic studies have shown that in addition to target disease-specific effects, vaccines have heterologous effects towards unrelated pathogens. Like some other vaccines, bacille Calmette-Guerin (BCG) has shown in observational studies and randomi

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

    OpenAIRE

    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

    2010-01-01

    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 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 ...

  18. The establishment of sub-strain specific WHO Reference Reagents for BCG vaccine

    OpenAIRE

    Dagg, Belinda; Hockley, Jason; Rigsby, Peter; Ho, Mei M.

    2014-01-01

    As the latest addition to the sub-strain specific WHO Reference Reagents of BCG vaccine, an international collaborative study was completed to evaluate the suitability of a candidate BCG Moreau-RJ sub-strain as a WHO Reference Reagent of BCG vaccine. This follows the recent replacement of the WHO 1st International Reference Preparation for BCG vaccine, by three sub-strain specific WHO Reference Reagents of BCG vaccine (Danish 1331, Tokyo 172-1 and Russian BCG-I) in order to complete the cover...

  19. 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.......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....

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

    OpenAIRE

    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 differen...

  1. 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

    2016-02-01

    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

  2. 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....

  3. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  4. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    Directory of Open Access Journals (Sweden)

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Full Text Available Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were previously BCG vaccinated and not-vaccinated, were included in this study. A total of sixty (60 vaccinated children and sixty non-vaccinated children were selected. These children were followed up prospectively for 24 months, at the end of which, it was seen whether they developed tuberculosis or not. Results: Out of these 60 children in both the cases and control groups, total number of BCG vaccinated children who developed TB were 4 (i.e. 6.6% and total number of Non-BCG vaccinated children who developed TB were 12 (i.e. 20%. Thus, the efficacy of BCG vaccine calculated in our study was 67%. Conclusion: Most studies in different parts of the world have shown that the efficacy of BCG vaccine varies from zero to eigh-ty percent. This study favors the efficacy of BCG vaccine. This vaccination strategy will be favorable for our children. Creation of awareness among the parents and family members for an early administration of BCG vaccine after child birth can be recom-mended.

  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. Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains.

    OpenAIRE

    Lagranderie, M R; Balazuc, A M; Deriaud, E; Leclerc, C D; Gheorghiu, M

    1996-01-01

    Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficiency, the choice of the vaccine strain may play an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used for BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated that a great difference ...

  8. Novel genome polymorphisms in BCG vaccine strains and impact on efficacy

    OpenAIRE

    Gao George; Alexander David C; Yu Xuping; Wu Zuowei; Tran Vanessa; Leung Andrea S; Zhu Baoli; Liu Jun

    2008-01-01

    Abstract Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify s...

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

    OpenAIRE

    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 recombin...

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

    OpenAIRE

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

    2011-01-01

    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. Her...

  11. Whole-Genome Sequences of Four Mycobacterium bovis BCG Vaccine Strains ▿

    OpenAIRE

    Pan, Yuanlong; Yang, Xi; Duan, Jia; Lu, Na; Leung, Andrea S.; Tran, Vanessa; Hu, Yongfei; Wu, Na; Liu, Di; Wang, Zhiming; Yu, Xuping; Chen, Chen; Zhang, Yuanyuan; Wan, Kanglin; LIU Jun

    2011-01-01

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.

  12. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    OpenAIRE

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were...

  13. Post BCG Lymphadenitis in Vaccinated Infants in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mostafa Behjati

    2008-12-01

    Full Text Available Objective: Bacille Calmette-Guَerin (BCG vacination is performed as a part of expanded program of immunization (EPI. Lymphadenitis is the most common complication of BCG vaccination. The aim of this study was to determine the incidence and natural course of BCG lymphadenitis vaccinated in Yazd, Iran.Methods: In this analytical prospective follow up study a total of 480 (240 females and 240 males consecutive newborns received 0.05 ml of BCG vaccine intradermally on right arm within the first week of life during April to July 2003. These babies were followed up when 1.5, 3, 4.5, 6 and 9 months old. Findings: A total of 26 (5.8% cases of lymphadenitis were detected. Lymphadenitis occurred as ipsilateral axillary nodes in 24 (92.3% cases, supraclavicular in one (3.8% case, and supraclavicular in association with axillary nodes in one case (3.8%. Infants developed lymphadenitis during 4 wks of life in one (3.84% case, between first and fourth month of life in 14 (53.8% cases, and between fourth and sixth month of life in 11 (42.3% cases. All 26 cases of lymphadenitis were followed up for 9 months. Twenty two (84.6% cases were simple or non-suppurative and 4 (15.4% cases suppurative lymphadenitis. Eleven (42.3% cases of non-suppurative lymphadennitis showed spontanous resolution and eleven (42.3% cases had partial regression without progression or drainage. Four (15.4% cases developed suppuration with one (3.8% case of fistulation and drainage. Conclusion: The greater incidence of lymphadenopathy in our cases can probably be attributed to a more immunogenic vaccine (Pasteur institute, Tehran, young vaccinees (newborn infants, injection in the right arm or improper dilution. Non-suppurative BCG lymphadenitis is a benign condition and regresses spontanously without any treatment.

  14. Delaying BCG Vaccination Until 8 Weeks of Age Results in Robust BCG-Specific T-Cell Responses in HIV-Exposed Infants

    OpenAIRE

    Tchakoute, Christophe Toukam; Hesseling, Anneke C.; Kidzeru, Elvis B.; Gamieldien, Hoyam; Passmore, Jo-Ann S.; Jones, Christine E.; Gray, Clive M.; Sodora, Donald L.; Jaspan, Heather B.

    2014-01-01

    Background. BCG vaccination prevents disseminated tuberculosis in children, but it is contraindicated for persons with human immunodeficiency virus (HIV) infection because it can result in severe disease in this population. In tuberculosis-endemic regions, BCG vaccine is administered soon after birth, before in utero and peripartum HIV infection is excluded. We therefore assessed the immunogenicity of BCG vaccine in HIV-exposed infants who received BCG at birth or at 8 weeks of age.

  15. Mycobacterium bovis BCG Vaccines Exhibit Defects in Alanine and Serine Catabolism

    OpenAIRE

    Chen, Jeffrey M.; Alexander, David C.; Behr, Marcel A.; LIU Jun

    2003-01-01

    Mycobacterium bovis BCG is the only accepted vaccine for the prevention of tuberculosis (TB) in humans. BCG is a live vaccine, and induction of immunity to TB requires productive infection of the host by BCG. However, BCG is not a satisfactory vaccine, because it fails to protect against pulmonary TB in adults. In this study, we found that BCG strains cannot utilize many naturally occurring amino acids as the sole nitrogen source for growth. This defect is caused, at least partially, by the l...

  16. 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; Rodrigues, A; Jensen, K J; Ravn, H; Allen, K J; Aaby, Peter

    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....

  17. 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; Andersen, Andreas; Eriksen, Helle Brander; Barbosa, Amarildo Gomes; Kantsø, Bjørn; Aaby, Peter; Benn, Christine Stabell

    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 on the...... 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...... previous finding, we wanted to test our a priori hypothesis that OPV would dampen the immune response to BCG, and secondarily to test immune responses to other antigens. METHODS: The study was conducted at the Bandim Health Project in Guinea-Bissau in 2009-2010. Infants were randomised to OPV0+BCG versus...

  18. New vaccines against tuberculosis: lessons learned from BCG immunisation in Brazil.

    Science.gov (United States)

    Antas, P R Z; Castello-Branco, L R R

    2008-07-01

    The current tuberculosis (TB) vaccine Mycobacterium bovis BCG has been employed for some 70 years in Brazil and lessons from its use should be taken in account for the development or improvement of new TB vaccines. The vast majority of the current population has been vaccinated with BCG, with the possible requirement for a booster immunisation in adulthood for TB protection. BCG Moreau strain also protects against leprosy, meningitis and extrapulmonary forms of TB. Factors related to differences in strain, dosage and BCG administering protocol have been responsible for the variable efficacy of BCG. This vaccine is clearly affected by, as yet unclear, host and/or environmental variables. In this brief review, we describe some aspects of BCG immunisation observed in Brazil that may be of importance for improving or replacing BCG. PMID:18440575

  19. [Comparative study of two dried intradermal BCG vaccines (author's transl)].

    Science.gov (United States)

    Fillastre, C; Guerin, N; Danusantoso, H; Sardadi, S

    1979-01-01

    Two BCG vaccines prepared from the same strain were studied clinically in Indonesia and in France. The concentration in culturable particles was comparable. Observed differences in the Mantoux results are discussed. The French results, based on use in a temperate climate by a specialized team, on well nourished children, appear better than the Indonesian findings. Further steps should be undertaken to improve results in Indonesia. PMID:539694

  20. In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG

    OpenAIRE

    Venkataswamy, Manjunatha M.; Goldberg, Michael F.; Baena, Andres; Chan, John; Jacobs, William R.; Porcelli, Steven A.

    2011-01-01

    The varied rates of protection induced by Mycobacterium bovis BCG vaccine against tuberculosis has been attributed to many factors such as genetic variability among BCG strains, rapid clearance of BCG in some populations, and different levels of previous exposure of vaccinated populations to environmental mycobacteria. However, the methods and conditions employed to prepare this vaccine for human usage by various manufacturers have not been investigated as potential factors contributing to th...

  1. Differential Effects of Prior Exposure to Environmental Mycobacteria on Vaccination with Mycobacterium bovis BCG or a Recombinant BCG Strain Expressing RD1 Antigens

    OpenAIRE

    Demangel, Caroline; Garnier, Thierry; Rosenkrands, Ida; Cole, Stewart T.

    2005-01-01

    In silico analysis reveals that most protective antigens expressed by the antituberculous vaccine Mycobacterium bovis BCG (BCG) are conserved in M. avium, supporting the hypothesis that exposure to environmental mycobacteria generates cross-reactive immune responses blocking BCG activity. We investigated the impact of sensitization with M. avium, M. scrofulaceum, or M. vaccae on the protective efficacy of a recombinant BCG strain expressing RD1 antigens (BCG::RD1), using a mouse model of expe...

  2. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    Science.gov (United States)

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation. PMID:18439875

  3. 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. PMID:25138291

  4. Protective efficacy of BCG vaccine against leprosy in southern Malaŵi.

    OpenAIRE

    Baker, D. M.; Nguyen-Van-Tam, J. S.; Smith, S J

    1993-01-01

    This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malaŵi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be conside...

  5. Immunogenicity of Mycobacterium tuberculosis Antigens in Mycobacterium bovis BCG-Vaccinated and M. bovis-Infected Cattle

    OpenAIRE

    Mustafa, A. S.; Skeiky, Y A; Al-Attiyah, R.; Alderson, M. R.; Hewinson, R. G.; Vordermeier, H M

    2006-01-01

    The development of novel vaccine strategies supplementing Mycobacterium bovis BCG (BCG) constitutes an urgent research challenge. To identify potential subunit vaccine candidates, we have tested a series of eight recently identified Mycobacterium tuberculosis antigens in M. bovis-infected and BCG-vaccinated cattle. These antigens were characterized on the basis of their ability to induce in vitro gamma interferon responses in infected or BCG-vaccinated calves. We were able to establish a hier...

  6. BCG and New Preventive Tuberculosis Vaccines: Implications for Healthcare Workers.

    Science.gov (United States)

    Hatherill, Mark; Scriba, Thomas J; Udwadia, Zarir F; Mullerpattan, Jai B; Hawkridge, Anthony; Mahomed, Hassan; Dye, Christopher

    2016-05-15

    Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosis-endemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs. PMID:27118856

  7. Genome Sequence of Mycobacterium bovis BCG Moreau, the Brazilian Vaccine Strain against Tuberculosis

    OpenAIRE

    Gomes, Leonardo H. F.; Otto, Thomas D; Vasconcellos, Érico A.; Ferrão, Patrícia M.; Maia, Renata M.; Moreira, Aline S.; Ferreira, Marcelo A.; Castello-Branco, Luiz R. R.; Degrave, Wim M.; Mendonça-Lima, Leila

    2011-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis, and the strains used worldwide represent a family of daughter strains with distinct genotypic characteristics. Here we report the complete genome sequence of M. bovis BCG Moreau, the strain in continuous use in Brazil for vaccine production since the 1920s.

  8. 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.

  9. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Science.gov (United States)

    Mostaan, Saied; Yazdanpanah, Bahador; Moukhah, Rasool; Hozouri, Hamid Reza; Rostami, Manouchehr; Khorashadizadeh, Mohsen; Zerehsaz, Javad; Mahabadi, Ramin Pirhajati; Saadi, Arya; Khanahmad, Hossein; Pooya, Mohammad

    2016-01-01

    Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants’ meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods.

  10. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant.

    Science.gov (United States)

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-01-01

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis was made based on the history, histopathology and virological studies. We suggest, although very rare, a BCG disease should be considered as a differential diagnosis in case of chest wall abscess, even if this is presenting as a hot abscess and even in immunocompetent infants if their age is related to BCG vaccination complications. PMID:25887440

  11. Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

    Directory of Open Access Journals (Sweden)

    Kátia da Silva Calabrese

    1992-01-01

    Full Text Available Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies.

  12. 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

  13. Assessment of immune response to repeat stimulation with BCG vaccine using in vitro PBMC model

    OpenAIRE

    Kashyap, Rajpal S; Husain, Aliabbas A.; Morey, Shweta H; Panchbhai, Milind S.; Deshpande, Poonam S; Purohit, Hemant J.; Taori, Girdhar M.; Daginawala, Hatim F.

    2010-01-01

    Background Tuberculosis (TB) is one of the most prevalent cause of death due to a single pathogen. Bacillus Calmette Guérin (BCG) is the only vaccine available for clinical use that protects against miliary TB; however, this vaccine has shown variable levels of efficacy against pulmonary TB. In India, a single dose of BCG vaccine is given and there are few countries where repeated doses of BCG are given. The incidence of TB in India is very high inspite of primary vaccination in neonatal peri...

  14. Vaccination of Cattle with a CpG Oligodeoxynucleotide-Formulated Mycobacterial Protein Vaccine and Mycobacterium bovis BCG Induces Levels of Protection against Bovine Tuberculosis Superior to Those Induced by Vaccination with BCG Alone

    OpenAIRE

    Wedlock, D. Neil; Denis, Michel; Skinner, Margot A.; Koach, Jessica; de Lisle, Geoffrey W.; Vordermeier, H. Martin; Hewinson, R Glyn; van Drunen Littel-van den Hurk, Sylvia; Babiuk, Lorne A.; Hecker, Rolf; Buddle, Bryce M.

    2005-01-01

    The development of a subunit protein vaccine for bovine tuberculosis which could be used either in combination with Mycobacterium bovis BCG (to improve the efficacy of that vaccine) or alone would offer significant advantages over currently available strategies. A study was conducted with cattle to determine the protective efficacy of a strategy based on concurrent immunization with an M. bovis culture filtrate (CFP) vaccine and BCG compared to vaccination with either vaccine alone. One group...

  15. 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.

  16. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

    OpenAIRE

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history ...

  17. Assessment of immunological markers and booster effects of Ag85B peptides, Ag85B, and BCG in blood of BCG vaccinated children: a preliminary report

    OpenAIRE

    Husain, Aliabbas A.; Daginawala, Hatim F.; Singh, Lokendra; Kashyap, Rajpal S

    2016-01-01

    Purpose In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette–Guérin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. Materials and Methods Fifty children from 1 month to 18 years of age were randomized for the s...

  18. Comparison of IFN-gamma responses to mycobacterial antigens as markers of response to BCG vaccination.

    Science.gov (United States)

    Weir, Rosemary E; Fine, Paul E M; Floyd, Sian; Stenson, Sally; Stanley, Carolynne; Branson, Keith; Britton, Warwick J; Huygen, Kris; Singh, Mahavir; Black, Gillian; Dockrell, Hazel M

    2008-01-01

    An increase in interferon-gamma (IFN-gamma) production to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), as measured in the cultured diluted whole blood assay, is one indicator of a protective immune response to BCG vaccine. We have explored the potential for this assay to be improved by measuring IFN-gamma responses to more defined antigens of M. tuberculosis (short-term and mid-term culture filtrates, ESAT-6, 38 kDa), Mycobacterium bovis (MPB70), M. bovis BCG (Antigen 85) and Mycobacterium leprae (35 kDa), in UK teenagers before and 1 year after BCG vaccination (or no vaccination as controls). There was a significant increase in response to the culture filtrates post-vaccination, but this was no greater than that to Mtb PPD. Many teenagers responded to the purified antigens, in particular to Antigen 85, prior to vaccination, and BCG vaccination could only augment this pre-existing response to a limited extent; prior exposure to environmental mycobacteria can thus induce cross-reactive responses to antigens which complicate interpretation of in vitro assays of vaccine response. In contrast, ESAT-6 was recognised by only one teenager prior to vaccination, and, as expected, responses were not boosted by BCG. We therefore conclude that Mtb PPD is the antigen preparation of choice for assessing the immunogenicity of BCG vaccination. PMID:18277396

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

    OpenAIRE

    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...

  20. Quality control of BCG vaccine by WHO: a review of factors that may influence vaccine effectiveness and safety.

    OpenAIRE

    Milstien, J. B.; J. J. Gibson

    1990-01-01

    WHO oversees the quality control of BCG vaccine via a system that includes regular testing of products by in vitro methods and clinical trials. Three parent strains of BCG (Glaxo-1077, Tokyo-172, and Pasteur-1173P2) account for over 90% of the vaccines currently in use worldwide. Important characteristics of the vaccine preparations are summarized here, along with their physical-chemical properties. In instances where diagnostic criteria for tuberculosis are stringent, there is no evidence th...

  1. Múltiplas doses de vacina BCG podem proteger contra asma? Can multiple doses of BCG vaccine protect against asthma?

    Directory of Open Access Journals (Sweden)

    Emanuel Sarinho

    2010-06-01

    Full Text Available OBJETIVO: Comparar a vacinação com uma única dose de BCG intradérmica com a vacinação com múltiplas doses, uma das quais pela técnica de multipuntura, em relação ao efeito protetor contra o aparecimento posterior de asma. MÉTODOS: Estudo de coorte retrospectivo com 2.311 pessoas vacinadas com BCG. Os indivíduos foram classificados de acordo com o número de doses de vacina BCG recebidas (uma dose, duas doses e três ou mais doses. O tempo mínimo de acompanhamento para verificar se houve algum efeito protetor da vacina BCG em relação ao diagnóstico de asma foi de 10 anos. RESULTADOS: A amostra incluiu 1.317 pessoas (56,99% que receberam apenas uma dose do BCG, 644 (27,87% que receberam duas doses e 350 (15,14% com três ou mais doses. O número de pacientes diagnosticados com asma entre aqueles que receberam uma dose de BCG, duas doses e três ou mais doses foi, respectivamente, 216 (16,40%, 107 (16,61% e 50 (14,28%. Não houve diferenças significativas entre os grupos. CONCLUSÕES: Na amostra estudada, não foi observada uma redução na prevalência de diagnóstico de asma com a revacinação ou com o uso de múltiplas doses da vacina BCG.OBJECTIVE: To compare BCG vaccination involving a single intradermal dose and that involving multiple doses, one given with the multiple puncture technique, in terms of the protective effect against the subsequent onset of asthma. METHODS: A retrospective cohort study involving 2,311 individuals having received the BCG vaccine. The patients were classified according to the number of doses of BCG vaccine administered (one; two; or three or more. The minimum follow-up period in order to determine whether there was any protective effect of BCG vaccination regarding the diagnosis of asthma was 10 years. RESULTS: The sample included 1,317 individuals (56.99% who had received only one BCG dose, 644 (27.87% who had received two doses, and 350 (15.14% who had received three or more doses. The number

  2. 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.

  3. Prime-boost vaccination strategy with bacillus Calmette-Guérin (BCG) and liposomized alpha-crystalline protein 1 reinvigorates BCG potency.

    Science.gov (United States)

    Siddiqui, K F; Amir, M; Khan, N; Rama Krishna, G; Sheikh, J A; Rajagopal, K; Agrewala, J N

    2015-08-01

    Bacillus Calmette-Guérin (BCG) remains the only available and most widely administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to protect vaccinated individuals either from primary infection or reactivation of latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact remains that BCG imparts protection in children against the disease, indicating that BCG possesses a wide protective antigenic repertoire. However, its failure to impart protection in adulthood can be linked to its failure to generate long-lived memory response and elicitation of an inadequate immune response against latency-associated antigens. Therefore, to improve the protective efficacy of BCG, a novel vaccination strategy is required. Consequently, in the present study, we have exploited the vaccination potential of liposomized α-crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in the multi-functional [interferon (IFN)-γ(hi) /tumour necrosis factor (TNF)-α(hi) ] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted (BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of both central memory (CD44(hi) /CD62L(hi) ) and effector memory (CD44(hi) /CD62L(lo) ) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L exhibited significantly better protection than BCG, as evidenced by a reduction in the bacterial burden and histopathological data of the lungs. In essence, BCG-Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency. PMID:25845290

  4. BCG Δzmp1 vaccine induces enhanced antigen specific immune responses in cattle.

    Science.gov (United States)

    Khatri, Bhagwati; Whelan, Adam; Clifford, Derek; Petrera, Agnese; Sander, Peter; Vordermeier, H Martin

    2014-02-01

    Mycobacterium bovis (M. bovis) causes major economy and public health problem in numerous countries. In Great Britain, despite the use of a test-and-slaughter strategy, the incidence of bovine tuberculosis (bTB) in cattle has steadily risen in recent years. One strategy being considered to reduce the burden of bTB in cattle is the development of an efficient vaccine. The only current potentially available vaccine against tuberculosis, live attenuated M. bovis bacille Calmette-Guérin (BCG), has demonstrated variable efficacy in both humans and cattle and the development of improved vaccination strategies for cattle is a research priority. In this study we assessed the immunogenicity in cattle of two recombinant BCG strains, namely BCG Pasteur Δzmp1::aph and BCG Danish Δzmp1. By applying a recently defined predictive immune-correlate of protection (T cell memory responses measured by cultured ELISPOT), we have compared these two recombinant BCG with wild-type BCG Danish SSI. Our results demonstrated that both strains induced superior T cell memory responses compared to wild-type BCG. These data provide support for the prioritisation of testing BCG Danish Δzmp1 in vaccination/M. bovis challenge studies to determine its protective efficacy. PMID:24394444

  5. 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.

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

    OpenAIRE

    Sarman Singh; Manoj Kumar; Pragati Singh

    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 ...

  7. Mantoux test results and BCG vaccination status in TB-exposed children

    OpenAIRE

    Fadilah Harahap; Ridwan M. Daulay; Muhammad Ali; Wisman Dalimunthe; Rini Savitri Daulay

    2016-01-01

    Background Tuberculosis (TB) infection is highly prevalent in Indonesia. The source of transmission of TB to a child is usually via an adult with sputum smear-positive pulmonary tuberculosis. The Mantoux test is a diagnostic tool for tuberculosis infection. The BCG vaccine has been used for the prevention of TB, but its efficacy is still debated. Objective To assess for an association between Mantoux test results and BCG vaccination in children who had contact with adult pulmonary tuberculosi...

  8. Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

    NARCIS (Netherlands)

    H. Korthals Altes; F. Dijkstra; A. Lugnèr; F. Cobelens; J. Wallinga

    2009-01-01

    Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a cost-e

  9. Effect of BCG vaccination on the frequency of 90Sr-induced osteosarcoma development in rats

    International Nuclear Information System (INIS)

    Using BCG vaccinated white rats of no breed the frequency of the development of induced osteosarcomas has been determined. It is shown that BCG injection of 5 mg per animal leads to changes in the frequency of the development of neoplasms and their multiplicity only in males which have been vaccinated 20 days before sup(90)Sr injection. The BCG dose increase up to 10 mg per animal in case of injection 10 days prior to sup(90)Sr administering has been accompanied by the suppression of the tumoral process independently of sex of experimental animals

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

    Directory of Open Access Journals (Sweden)

    Sarman Singh

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    Singh, Sarman; Kumar, Manoj; 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

  12. 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.

  13. Evaluation of a Human BCG Challenge Model to Assess Antimycobacterial Immunity Induced by BCG and a Candidate Tuberculosis Vaccine, MVA85A, Alone and in Combination

    OpenAIRE

    Harris, Stephanie A.; Meyer, Joel; Satti, Iman; Marsay, Leanne; Poulton, Ian D; Tanner, Rachel; Minassian, Angela M; Helen A. Fletcher; McShane, Helen

    2013-01-01

    Background. A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection. Methods. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosi...

  14. The success and failure of BCG - implications for a novel tuberculosis vaccine.

    Science.gov (United States)

    Andersen, Peter; Doherty, T Mark

    2005-08-01

    Over the past 50 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has maintained its position as the world's most widely used vaccine, despite showing highly variable efficacy (0-80%) in different trials. The efficacy of BCG in adults is particularly poor in tropical and subtropical regions. Studies in animal models of TB, supported by data from clinical BCG trials in humans, indicate that this failure is related to pre-existing immune responses to antigens that are common to environmental mycobacteria and Mycobacterium tuberculosis. Here, we discuss the potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy. PMID:16012514

  15. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial

    OpenAIRE

    Benn, Christine Stabell; Fisker, Ane Bærent; Napirna, Bitiguida Mutna; Roth, Adam; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Ravn, Henrik; Yazdanbakhsh, Maria; Rodrigues, Amabelia; Whittle, Hilton; Aaby, Peter

    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. Intervention Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12...

  16. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  17. BCG Vaccination as a Prevention Strategy, Threats and Benefits

    Directory of Open Access Journals (Sweden)

    Shirvani

    2016-04-01

    Full Text Available Context Tuberculosis is still one of the deadliest communicable diseases. Objectives Nine million people worldwide developed TB in 2013, and 1.5 million people died from it, 360000 of which were HIV positive. Although the disease is controllable by means of diagnostic and treatment measures, the death toll from the disease is still high, and efforts to combat it must be accelerated. Data Sources Data compiled from 202 countries in the Global Tuberculosis Report 2014 showed that TB is present in all regions of the world. Study Selection Higher numbers of tuberculosis cases were diagnosed in 2013 in comparison with previous reports, indicating that diagnoses and reports of new cases may be improved by stringent data collection. Data Extraction A special note to the 2014 report highlighted the progress of drug resistant TB during the last two decades. Results Worldwide, a proportion of new cases with multidrug-resistant TB (MDR-TB were reported at 3.5% in 2013 without a significant change compared with recent years. Interestingly, higher levels of resistance and poor treatment outcomes are of major concern in some parts of the world. Due to this concern, special attention is focused on prevention rather than treatment. On the other hand, the effectiveness of an existing vaccine (BCG is increasingly questionable. Conclusions It has the potential to cause disseminated infection, and an increasing number of immunocompromised patients prone to disease and the suboptimal preventive potency of this vaccine suggest the need for a global attempt to review its benefits and disadvantages.

  18. Failure of the Mycobacterium bovis BCG Vaccine: Some Species of Environmental Mycobacteria Block Multiplication of BCG and Induction of Protective Immunity to Tuberculosis

    OpenAIRE

    Brandt, L.; cunha, jf; olsen, aw; Chilima, B.; Hirsch, P; Appelberg, R; Andersen, P.

    2002-01-01

    The efficacy of Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG va...

  19. 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;

    interpretation of cases of illness and atopic diseases in their personal network and family to evaluate risk for their child to develop atopic diseases or get hospitalised. This lay epidemiologi forms the basis for their decision. Davison C, Frankel S, Davey Smith G. Inheriting heart trouble: the relevance of......Introduction: In a large prospective randomised clinical trial in Denmark we are testing 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 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 with...

  20. Lactoferrin Augmentation of the BCG Vaccine Leads to Increased Pulmonary Integrity

    OpenAIRE

    Actor, Jeffrey K.; Shen-An Hwang; Kruzel, Marian L.; Welsh, Kerry J.

    2011-01-01

    The goal of vaccination to prevent tuberculosis disease (TB) is to offer long-term protection to the individual and the community. In addition, the success of any protective TB vaccine should include the ability to limit cavitary formation and disease progression. The current BCG vaccine protects against disseminated TB disease in children by promoting development of antigenic-specific responses. However, its efficacy is limited in preventing postprimary pulmonary disease in adults that is re...

  1. Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral Mycobacterium bovis BCG Immunization against Pulmonary Tuberculosis

    OpenAIRE

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-01-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to...

  2. WHO Informal Consultation on standardization and evaluation of BCG vaccines Geneva, Switzerland 22-23 September 2009.

    Science.gov (United States)

    Ho, Mei M; Southern, James; Kang, Hye-Na; Knezevic, Ivana

    2010-10-01

    The current World Health Organization Requirements for BCG vaccine are in need of revision to address the diversity of sub-strains used for production, potential improvements of quality control assays for lot release, and the establishment of sub-strain specific Reference Reagents. A consultation meeting was organized to discuss issues regarding the standardization and evaluation of BCG vaccines in the forum of regulators, BCG vaccine manufacturers, developers of selected new live tuberculosis (TB) vaccines and researchers. The development of new recombinant BCG and live attenuated TB vaccines and the characterisation of different BCG sub-strains using state-of-the-art technologies were also reviewed. The objective of the meeting was to revise and update the current recommendations focused on the scope, terminology, manufacturing issues, and the incorporation of new reference reagents and new quality control tests. PMID:20692219

  3. A Comprehensive Survey of Single Nucleotide Polymorphisms (SNPs) across Mycobacterium bovis Strains and M. bovis BCG Vaccine Strains Refines the Genealogy and Defines a Minimal Set of SNPs That Separate Virulent M. bovis Strains and M. bovis BCG Strains▿ †

    OpenAIRE

    Garcia Pelayo, M. Carmen; Uplekar, Swapna; Keniry, Andrew; Mendoza Lopez, Pablo; Garnier, Thierry; Nunez Garcia, Javier; Boschiroli, Laura; Zhou, Xiangmei; Parkhill, Julian; Smith, Noel; Hewinson, R Glyn; Cole, Stewart T.; Gordon, Stephen V.

    2009-01-01

    To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccine Mycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains of Mycobacterium bovis and M. bovis BCG. SNPs were assayed in M. bovis isolates from France and the United Kingdom and from different BCG vaccines in order to identify those that arose during the attenuation process which gave rise to BCG. Informative data sets...

  4. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

  5. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  6. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis.

    Science.gov (United States)

    Taus, Francesco; Santucci, Marilina B; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  7. 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

    delayed BCG, the manufacturer of the BCG vaccine experienced a period with relatively slow growth rate of the BCG. We investigated the association between growth rate of BCG when manufacturing the vaccine and its capability to induce immune responses in vivo and in vitro. METHODS: 1633 neonates were......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...... production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482)....

  8. 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; Poulsen, Anja; Gustafson, Per; Gomes, Justino; Djana, Queba; Jakobsen, Marianne; Garly, May-Lill; Rodrigues, Amabelia; Aaby, Peter

    2005-01-01

    The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and......=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...

  9. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  10. [A case diagnosed with chronic granulomatous disease after disseminated infection following BCG vaccination].

    Science.gov (United States)

    Delibalta, Güler; Seringeç, Murat; Öncül, Oral

    2015-07-01

    BCG (Bacillus Calmette-Guérin) vaccine is a widely used vaccine with the recommendation of World Health Organization to protect children against miliary tuberculosis (TB) and TB meningitis. Severe side effects related to this vaccine mostly manifest in the presence of underlying immunosuppressive disease. In this report, an infant case with unknown chronic granulomatous disease (CGD) who developed disseminated BCG infection after administration of BCG vaccine, was presented. High fever, left axillary lymphadenopathy and hepatosplenomegaly have developed in a 3-month 28-day female infant, without a known health problem, following BCG vaccination. The acid-fast bacilli (ARB) was isolated from the material of excised lymph node cultivated in Löwenstein-Jensen medium, and the isolate was identified as Mycobacterium bovis. Mycobacterium tuberculosis complex DNA was detected in the axillary lymph node sample by polymerase chain reaction. Anti-tuberculous treatment included 20 mg/kg of rifampicin+10 mg/kg of isoniazid+15 mg/kg of ethambutol+30 mg/kg of streptomycin was started. The patient was then further evaluated for immunodeficiency and on the basis of the results of dihydroamine and LAD (lymphocyte adhesion defect) tests, diagnosed as autosomal recessive CGD. Based on the anamnesis, there was no known immunodeficiency history both in the case during neonatal period and her family members. Interferon-gamma therapy, which is recommended for the patients with CGD living in endemic areas, was initiated. Our patient's fever dropped at the 15th day of anti-tuberculosis treatment, and she was discharged on the 35th day and continued to receive treatment at home. The patient was followed up at outpatient clinic and had no additional complaints; her hepatosplenomegaly was back to normal at the third month. As a result, since BCG vaccine is contraindicated in CGD carriers, newborns with a family history of CGD should be immunologically examined and BCG vaccine should be

  11. Draft Genome Sequence of the Vaccination Strain Mycobacterium bovis BCG S4-Jena.

    Science.gov (United States)

    Wibberg, Daniel; Winkler, Anika; Straube, Eberhard; Karrasch, Matthias; Keller, Peter M; Kalinowski, Jörn

    2016-01-01

    Here, we present the draft genome sequence of ITALIC! Mycobacterium bovisBCG S4-Jena, a tuberculosis vaccine strain. The genome of S4-Jena is represented by 48 scaffolds, consisting of 132 scaffolded contigs and amounting to a size of about 4.2 Mb. New genes potentially encoding a phage fragment were identified in the genome. PMID:27103721

  12. BCG Moreau Rio de Janeiro: an oral vaccine against tuberculosis - review

    OpenAIRE

    Thereza Christina Benévolo-de-Andrade; Renata Monteiro-Maia; Catherine Cosgrove; Luiz Roberto R Castello-Branco

    2005-01-01

    The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of ora...

  13. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components. PMID:7505240

  14. 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

    2015-09-01

    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

  15. Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life.

    Science.gov (United States)

    Yang, Junhua; Qi, Fangfang; Gu, Huaiyu; Zou, Juntao; Yang, Yang; Yuan, Qunfang; Yao, Zhibin

    2016-01-01

    Bacillus Calmette-Guérin (BCG) is administered to neonates worldwide, but it is still unknown whether this neonatal vaccination affects brain development during early postnatal life, despite the close association of the immune system with the brain. Newborn C57BL/6 mice were injected subcutaneously with BCG or phosphate-buffered saline (PBS) and their mood status and spatial cognition were observed at four and eight weeks (w) old. The mice were also subjected to tests at 2 and 6 w to examine BCG's effects on neurogenesis, the hippocampal microglia phenotype and number, and the expression of hippocampal neuroimmune molecules and peripheral cytokines. The BCG-injected mice showed better behavioral performances at 4 w. We observed elevated neurogenesis, M2 microglial activation and a neurotrophic profile of neuroimmune molecules [more interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor (TGF)-β, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1 and less tumor necrosis factor (TNF)-α and IL-1β] in the hippocampus of the 2-w-old BCG-mice. In the periphery, BCG induced a T helper (Th)-1 serum response. At the individual level, there were positive correlations between the serum IFN-γ/IL-4 ratio and the levels of neurotrophins and neurogenesis in the hippocampus. These findings suggest that neonatal BCG vaccination improved neurogenesis and mouse behavior in early life by affecting the neuroimmune milieu in the brain, which may be associated with a systemic Th1 bias. PMID:26536170

  16. 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 delay

  17. Protective effect of bacillus Calmette Guιrin (BCG vaccine in the prevention of leprosy: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Zodpey Sanjay

    2007-01-01

    Full Text Available Background: Although the role of bacillus Calmette Guιrin (BCG vaccine in the prevention of leprosy was hypothesized as early as 1939, its level of protective effect remained controversial. Aim: As a meta-analysis systematically combines the results from different studies, we summarize the protective effect of BCG vaccine in prevention of leprosy using meta-analytic procedures. Methods: Our search strategy included a computerized literature search, snowballing technique to identify potential studies, review of previously compiled lists of BCG studies and articles, contacting experts on BCG vaccination and manual search to locate articles in non-indexed journals. The present meta-analysis included 22 studies (6 trials, 2 cohort studies and 14 case-control studies on the role of BCG vaccine in the prevention of leprosy. The random effects model as described by DerSimonian and Laird was used to summarize the effect measures. For each summarization, a Chi-square test of heterogeneity was estimated. To strengthen the viewpoint further additional information from the studies which were not included in meta-analysis, was also utilized. Results: The summary protective effects calculated from trials, cohort studies and case-control studies were 43 (27-55, 62 (53-69 and 58 (47-67% respectively, which were statistically significant. These estimates confirmed the protective association between BCG vaccination and leprosy. Review of 29 studies focusing on the role of BCG vaccination in the prevention of leprosy revealed that not a single study reported a negative protective effect. Thirteen (44.8% studies demonstrated greater than or equal to 50% efficacy/effectiveness. Conclusion: There is sufficient and convincing evidence of the protective effect of BCG vaccine against leprosy, as reflected from the meta-analysis and overall review of 29 studies of BCG vaccination and leprosy.

  18. 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. PMID:26795364

  19. Size characterization of Mycobacterium bovis BCG (Bacillus Calmette Guérin) vaccine, Tice substrain.

    Science.gov (United States)

    Zhang, A; Groves, M J

    1988-09-01

    Reconstituted, lyophilized, attenuated Mycobacterium bovis, Bacillus Calmette Guérin (BCG) vaccine, Tice substrain, was characterized using a Coulter Multisizer and a HIAC/Royco counter. The primary organism has an equivalent spherical diameter approximating 1 micron but the BCG cell suspension is heavily aggregated. The cumulative size distribution of the suspension fits a log-probit plot and this information can be used to determine the total number of particles per ampoule. The instrumental count may be related to the viable count. The state of dispersion was unaffected by mild shear (syringe aspiration or ultrasound) and only slightly affected by the addition of cetylpyridinium chloride or sodium tauroglycolate. PMID:3073388

  20. Enhanced Protection against Bovine Tuberculosis after Coadministration of Mycobacterium bovis BCG with a Mycobacterial Protein Vaccine-Adjuvant Combination but Not after Coadministration of Adjuvant Alone▿

    OpenAIRE

    Wedlock, D. Neil; Denis, Michel; Painter, Gavin F; Ainge, Gary D.; Vordermeier, H. Martin; Hewinson, R Glyn; Buddle, Bryce M.

    2008-01-01

    Current efforts are aimed at optimizing the protective efficacy of Mycobacterium bovis BCG by the use of vaccine combinations. We have recently demonstrated that the protection afforded by BCG alone is enhanced by vaccinating cattle with a combination of vaccines comprising BCG and a protein tuberculosis vaccine, namely, culture filtrate proteins (CFPs) from M. bovis plus an adjuvant. In the current study, three different adjuvant systems were compared. The CFP was formulated with a depot adj...

  1. 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

    . METHODS: Two-thousand three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG" (intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N = 1717) were included in a two-by-two randomised trial in which they were additionally randomised 1:1 to vitamin A...... 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...

  2. A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

    Science.gov (United States)

    da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

  3. Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

    OpenAIRE

    Hwang, Shen-An; Wilk, Katarzyna M.; Budnicka, Monika; Olsen, Margaret; Bangale, Yogesh A.; Hunter, Robert L.; Kruzel, Marian L.; Actor, Jeffrey K.

    2007-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world’s population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous repor...

  4. 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.

  5. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination.

    Science.gov (United States)

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features ("fried eggs" colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

  6. 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......BACKGROUND:  Bacillus Calmette-Guérin (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 Guinea...... 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...

  7. Distribution of 35S-labelled BCG after application to the camera oculi anterior of BCG vaccinated and non-vaccinated rabbits

    International Nuclear Information System (INIS)

    After application of 35S-labelled BCG to the camera oculi anterior of the rabbit, the escape pathways of germs and their quantitative and qualitative distribution in eyes and blood has been studied in BCG-vaccinated and non-vaccinated animals while varying the amount of germs applied. As criteria, 35S concentration and the amount of 35S in ocular sections and in the blood which can be identified by means of distributing germs under the chosen conditions, have been detected. After only 10 minutes, elimination of germs is to be seen, continuing for a period longer than the 2 hours of post-injection period observed. Relatively high 35S concentrations indicate a long-term storage in the iris and in the ciliary body. The flow continues regularly but restrained via choroid and sclera into the blood. Flow velocity depends only within specific limits on the amount of germs injected into the anterior chamber. Under study conditions the flow mode via N.opticus and via lymphs is rather unimportant. The rest of the germs are distributed in the organism via blood vessels. A comparison of 35S concentration in sections of both eyes shows germ enrichment in tissues with sufficient blood supply, particularly in the choroid. Differences in germ distribution in vaccinated and non-vaccinated animals are not to be seen in the 35S distribution pattern. Neither higher nor lower germ doses indicate a stronger retention in the ocular sections of vaccinated animals. The necessity to complete this study by applying germ doses smaller than 1 mg (humidity weight) is stated pointing out technical difficulties involved while applying a test model. (orig.)

  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

    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 in...... MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age < 37 weeks) completed an ASQ at 6 and 22 months. Developmental assessment was available for 3453/4262 (81%). RESULTS: The...... -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. Effects of diet and genetics on Mycobacterium bovis BCG vaccine efficacy in inbred guinea pigs.

    OpenAIRE

    Cohen, M K; Bartow, R A; Mintzer, C L; McMurray, D. N.

    1987-01-01

    Strain 2 and strain 13 guinea pigs were vaccinated with Mycobacterium bovis BCG and placed on low-protein or protein-adequate diets. Five weeks later all animals were infected by the respiratory route with virulent Mycobacterium tuberculosis H37Rv organisms. Four weeks postchallenge, guinea pigs were skin tested with purified protein derivative and sacrificed. Protein deficiency resulted in significant reductions in body weight and thymus weight and in an impairment in the ability to control ...

  10. "PRESUMED SYSTEMIC BACILLE CALMETTE-GUÉRIN DISEASE AFTER BCG VACCINATION: REPORT OF A CLINICAL CASE "

    Directory of Open Access Journals (Sweden)

    P. Tabatabaie

    2006-08-01

    Full Text Available BCG (bacille Calmette–Guérin vaccine is administered worldwide to prevent severe forms of tuberculosis. It is considered to be safe; however, occasional complications are seen. The most serious complication is BCGosis. We report a case of BCGosis with granulomatous hepatitis and acid-fast bacilli in liver and spleen. We treated the patient with antituberculosis drugs without any response to treatment.

  11. 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. PMID:26266551

  12. 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.

  13. Epidemiological significance of the local reaction to direct BCG vaccination as assessed from a study in Mongolia.

    Science.gov (United States)

    Chavganc, J; Hanák, R; ten Dam, H G

    1969-01-01

    Direct BCG vaccination has considerable operational advantages over the classical method of vaccinating only persons who do not react to tuberculin. In the present study it is shown that the direct method as applied in Mongolia does not cause any untoward reactions in persons who react to tuberculin and therefore can be considered a rational public health procedure.By reason of the repeated follow-up examinations, it was possible to obtain a clear picture of the development of the local BCG reactions and to test the hypothesis that these reactions may give information on pre-existing tuberculin sensitivity. It appeared impossible to deduce with any accuracy from either the local induration or the tissue destruction at the site of vaccination whether a person had tuberculin sensitivity before vaccination or not, and the results obtained with 2 different vaccines were inconsistent. It is therefore concluded that the local BCG reaction has no epidemiological significance in this respect. PMID:5309085

  14. 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. PMID:26896668

  15. The effect of tuberculin skin test and BCG vaccination on the expansion of PPD-specific IFN-gamma producing cells ex vivo.

    Science.gov (United States)

    Ota, Martin O C; Brookes, Roger H; Hill, Philip C; Owiafe, Patrick K; Ibanga, Hannah B; Donkor, Simon; Awine, Timothy; McShane, Helen; Adegbola, Richard A

    2007-12-17

    Understanding the immunogenicity of BCG in a population where it has failed will facilitate the design of new TB vaccines. We assessed the immunogenicity of M. bovis BCG over 12 months by ELISPOT assay. Forty-one adolescents and young Gambian male adults received a tuberculin skin test (TST) which was followed one week later by BCG vaccination, but the 23 control subjects received neither of these. TST alone significantly induced PPD-specific IFN-gamma producing cells. Twenty-three percent of subjects did not respond to BCG, which was associated with higher pre-existing ex vivo response to PPD. Paradoxically, amongst BCG responders there was a correlation between pre-existing response and subsequent response to BCG. We conclude that BCG is immunogenic, but this effector response is short-lived and can be limited in higher pre-existing anti-mycobacterial immunity, suggesting a possible threshold beyond which BCG immunogenicity is inhibited. PMID:18023944

  16. BCG LYMPHADENITIS

    Directory of Open Access Journals (Sweden)

    Vijayakumar

    2014-08-01

    Full Text Available Background: The World Health Organization (WHO has recommended Bacillus Calmette-Guerin (BCG vaccination as a part of the global expanded program for immunization. Although the BCG vaccine is usually a safe vaccine, a number of complications with lymphadenitis being the most common complication, can occur. AIM: The aim of the present study was to evaluate the clinical presentation and the histomorphological features of BCG adenitis in children. RESULTS: A total of 60 patients with BCG lymphadenitis presented between June 2010 and December 2013. The most common age of presentation was 3 months. In the majority (50 of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 5 (8.3% patients, and both the left axillary and supraclavicular lymph nodes were involved in 5 cases (8.3%. All the patients had history of BCG vaccination prior to the onset of lymphadenitis. CONCLUSION: Diagnosis of BCG lymphadenitis is clinical. Parental education and awareness among paramedical personnel, including general practitioners, is essential so that prompt recognition and management of BCG adenitis can be ensured.

  17. 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.; van de Sande, P.J.M.; Whittle, H.; Fisker, Bent; Roth, A.; Aaby, Peter; Yazdanbakhsh, M.; Benn, Christine Stabell

    2010-01-01

    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...

  18. The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda

    OpenAIRE

    Anderson, Elizabeth J.; Webb, Emily L.; Mawa, Patrice A.; Kizza, Moses; Lyadda, Nancy; Nampijja, Margaret; Elliott, Alison M

    2012-01-01

    Background Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. Methods Infants from the Ente...

  19. A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    OpenAIRE

    Kernodle, Douglas S.; Cynamon, Michael H.; Gates, Hiriam O.; Alexandria D. Allen; Miriam Braunstein; Kyi-Toe Tham; Shoen, Carolyn M.; Michelle S. DeStefano; Hager, Cynthia C.

    2013-01-01

    Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune...

  20. Theoretical and methodological aspects of BCG vaccine from the discovery of Calmette and Guérin to molecular biology. A review.

    Science.gov (United States)

    Lugosi, L

    1992-10-01

    The BCG vaccine has been used to prevent tuberculosis since 1921 and applied for immunostimulation in neoplasia since the 1960s. Both the preventive and immunostimulation effects have been evaluated and communicated with contradictory, positive and negative conclusions. For an objective evaluation and interpretation of the protective efficacy, effectiveness and efficiency of the BCG vaccination it must be considered that: (1) several BCG substrains have been developed in manufacturing laboratories that differ in the residual virulence which determines immunogenicity and reactogenicity; (2) various liquid and freeze-dried BCG vaccine production methods are used, resulting in different BCG viable units per dose; (3) quantitative bioassay methods are not yet being used for statistical quality control of the vaccine; (4) BCG products are applied in various demographical, epidemiological and socioeconomic conditions with different vaccination policies; (5) inadequate biostatistical models are often used to analyse efficacy, effectiveness and adverse reactions. The same conditions influence the precise evaluation of BCG immunostimulation in neoplasia. Recombinant DNA technology will modify production methods, and explain at the molecular level the mechanism of the protective effects BCG confers in tuberculosis and immunostimulation in neoplasia. High level laboratory techniques and biostatistical methods, based on probability logic and inductive inference, ensure appropriate experimental designs and the exact analysis of laboratory data and the results of vaccination policies. They will lead to the evaluation of the protective effect of BCG in order to reduce the BCG contradictions. PMID:1493232

  1. 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. PMID:27060378

  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.......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. A novel recombinant BCG vaccine encoding eimeria tenella rhomboid and chicken IL-2 induces protective immunity against coccidiosis.

    Science.gov (United States)

    Wang, Qiuyue; Chen, Lifeng; Li, Jianhua; Zheng, Jun; Cai, Ning; Gong, Pengtao; Li, Shuhong; Li, He; Zhang, Xichen

    2014-06-01

    A novel recombinant Bacille Calmette-Guerin (rBCG) vaccine co-expressed Eimeria tenella rhomboid and cytokine chicken IL-2 (chIL-2) was constructed, and its efficacy against E. tenella challenge was observed. The rhomboid gene of E. tenella and chIL-2 gene were subcloned into integrative expression vector pMV361, producing vaccines rBCG pMV361-rho and pMV361-rho-IL2. Animal experiment via intranasal and subcutaneous route in chickens was carried out to evaluate the immune efficacy of the vaccines. The results indicated that these rBCG vaccines could obviously alleviate cacal lesions and oocyst output. Intranasal immunization with pMV361-rho and pMV361-rho-IL2 elicited better protective immunity against E. tenella than subcutaneous immunization. Splenocytes from chickens immunized with either rBCG pMV361-rho and pMV361-rho-IL2 had increased CD4(+) and CD8(+) cell production. Our data indicate recombinant BCG is able to impart partial protection against E. tenella challenge and co-expression of cytokine with antigen was an effective strategy to improve vaccine immunity. PMID:25031464

  4. Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis

    OpenAIRE

    Festjens, Nele; Bogaert, Pieter; Batni, Anjana; Houthuys, Erica; Plets, Evelyn; Vanderschaeghe, Dieter; Laukens, Bram; Asselbergh, Bob; Parthoens, Eef; De Rycke, Riet; Willart, Monique A.; Jacques, Peggy; Elewaut, Dirk; Brouckaert, Peter; Lambrecht, Bart N.

    2011-01-01

    Mycobacterium bovis bacille Calmette-Guerin (BCG) provides only limited protection against pulmonary tuberculosis. We tested the hypothesis that BCG might have retained immunomodulatory properties from its pathogenic parent that limit its protective immunogenicity. Mutation of the molecules involved in immunomodulation might then improve its vaccine potential. We studied the vaccine potential of BCG mutants deficient in the secreted acid phosphatase, SapM, or in the capping of the immunomodul...

  5. Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy ▿

    OpenAIRE

    Brynjolfsson, Siggeir F.; Bjarnarson, Stefania P.; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-01-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody ...

  6. 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. PMID:26544594

  7. BCG ADENITIS: ACTION OR INACTION?

    OpenAIRE

    Ashwin V; Shruti; De, Dipankar

    2014-01-01

    BCG adenitis, the enlargement of regional lymph nodes after BCG vaccination is one of the common complications seen. BCG adenitis may present at varied time interval after the vaccine administration. Different medical and surgical treatment modalities have been reported for its management. We report our management experience of BCG adenitis seen over a period of 1 year.

  8. An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2009-09-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products. PMID:19571109

  9. An Oral Mycobacterium bovis BCG Vaccine for Wildlife Produced in the Absence of Animal-Derived Reagents▿

    OpenAIRE

    Cross, Martin L; Lambeth, Matthew R.; Aldwell, Frank E.

    2009-01-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

  10. 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

  11. Comparative evaluation of booster efficacies of BCG, Ag85B, and Ag85B peptides based vaccines to boost BCG induced immunity in BALB/c mice: a pilot study

    OpenAIRE

    Husain, Aliabbas A.; Warke, Shubhangi R.; Kalorey, Dewanand R.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S

    2015-01-01

    Purpose In the present study booster efficacies of Ag85 B, Bacillus Calmette-Guerin (BCG), and Ag85B peptides were evaluated using prime boost regimes in BALB/c mice. Materials and Methods Mice were primed with BCG vaccine and subsequently boosted with Ag85B, BCG and cocktail of Ag85B peptides. Results Based on analysis of immune response it was observed mice boosted with Ag85B peptides showed significant (p < 0.001) cytokines levels (interferon γ, interleukin 12) and BCG specific antibodies ...

  12. Cellular immunity confers transient protection in experimental Buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination.

    Directory of Open Access Journals (Sweden)

    Alexandra G Fraga

    Full Text Available BACKGROUND: Buruli ulcer (BU is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN. BCG vaccination also resulted in cell-mediated immunity (CMI in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.

  13. Improved protection in guinea pigs after vaccination with a recombinant BCG expressing MPT64 on its surface

    Directory of Open Access Journals (Sweden)

    Simon O. Clark

    2015-01-01

    Full Text Available The lack of an efficient vaccine against tuberculosis is still one of the major problems threatening global human health. In previous work we showed that expression of the protective antigen MPT64 on the surface of Mycobacterium bovis BCG, the only approved vaccine against tuberculosis, strongly improved its immunogenicity and protective potential in mice. In this work we demonstrate that the same recombinant strain is able to induce better protection than wild type BCG also in guinea pigs preventing Mycobacterium tuberculosis dissemination and lung pathology, making this strain a strong candidate for further testing.

  14. Construction, Expression and Identification of a Recombinant BCG Vaccine Encoding Human Mycobacterium Tuberculosis Heat Shock Protein 65

    Institute of Scientific and Technical Information of China (English)

    戴五星; 梁靓; 高红; 黄海浪; 陈智浩; 程继忠; 皇甫永穆

    2004-01-01

    Heat shock protein 65 (HSP65) is one of the most important protective immunogens against the tuberculosis infection. The signal sequence of antigen 85B and the whole HSP65 DNA sequence of human Mycobacterium tuberculosis (M. tuberculosis) were amplified from BCG genome and plasmid pCMV-MTHSP65 respectively by polymerase chain reactions (PCR). These two sequences were cloned into the plasmid pBCG-2100 under the control of the promoter of heat shock protein 70 (HSP70) from human M. tuberculosis, yielding the prokaryotic shuttle expression plasmid pBCG-SP-HSP65. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis showed that the two cloned DNA sequences were consistent with those previously reported, and the direction of their inserting into the recombinant was correct and the reading frame had been maintained. The recombinants were electroporated into BCG to construct the recombinant BCG vaccine and induced by heating. The induced expression detected by SDS-PAGE showed that the content of 65 kD protein expressed in recombinant BCG was 35.69 % in total bacterial protein and 74.09 % in the cell lysate supernatants, suggesting that the recombinant HSP65 gene could express in BCG with high efficiency and the expressed proteins were mainly soluble. Western-blot showed that the secretive recombinant proteins could specifically combine with antibody against M.tuberculosis HSP65, indicating that the recombinant proteins possess the biological activity of HSP65.

  15. DIFFERENT CHARACTERISTICS OF INFECTION WITH MYCOBACTERIA IN GRANULOMA CELLS FROM MICE WITH LATENT TUBERCULOSIS INFECTION AND IN BONE MARROW AND PERITONEAL MACROPHAGES AFTER BCG VACCINE APPLICATION IN VITRO

    OpenAIRE

    E. G. Ufimtseva

    2014-01-01

    The aim of the study was to compare the content of BCG-mycobacteria in granulomas obtained from various organs of BALB/c mice with latent tuberculosis after in vivo exposure to BCG vaccine and in mouse bone marrow and peritoneal macrophages after BCG infection in vitro. The granuloma cells obtained from mice through 20 days, one and two months after their BCG-infecting in vivo were differed with respect to both the number of granulomas with macrophages containing the defined numbers of BCG-my...

  16. 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; Benn, Christine Stabell; Joosten, Leo A B; Jacobs, Cor; van Loenhout, Joke; Xavier, Ramnik J; Aaby, Peter; van der Meer, Jos W M; van Crevel, Reinout; Netea, Mihai G

    2013-01-01

    We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity......'. 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 postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase...

  17. The Mycobacterium bovis BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice.

    Science.gov (United States)

    Gu, Dongqing; Chen, Wei; Mi, Youjun; Gong, Xueli; Luo, Tao; Bao, Lang

    2016-04-01

    Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures. In conclusion, we for the first time, developed a protein- and plasmid DNA-based booster vaccine based on Rv0577. Our findings suggest that antigen Rv0577-based DNA vaccine is immunogenic and can efficiently boost BCG, which could be helpful in the design of an efficient vaccination strategy against TB. PMID:26922320

  18. Advances in the characterization of a proteol iposome derived from Mycobacterium bovis BCG as vaccine candidate against tuberculosis

    Directory of Open Access Journals (Sweden)

    Nadine Alvarez-Cabrera

    2014-12-01

    Full Text Available Despite efforts to eradicate tuberculosis (TB worldwide, this remains a serious health problem. The Bacillus Calmette-Guerin (BCG, the only available vaccine against TB, has variable efficacy and though protects against severe forms of the disease in childhood, has a questionable role in the protection against pulmonary tuberculosis in adults. In recent years, new TB vaccine candidates are being developed using multiple vaccine strategies. Taking into account the antigenic similarity of M. bovis BCG and M. tuberculosis, and the history of the use of proteoliposomes in vaccine formulations, we aimed to study the potentialities of a proteoliposome derived from M. bovis BCG (PLBCG as a potential vaccine candidate against TB. The results demonstrate that a PLBCG was obtained, which was observed by different techniques and that is composed of nanoparticulate vesicles. Additionally, analysis by SDSPAGE followed by Coomassie stained showed the presence of several protein bands on PLBCG whose molecular size may correspond with that reported for M. bovis BCG protein having homology to M. tuberculosis.

  19. Assessment of tuberculosis infection during treatment with biologic agents in a BCG-vaccinated pediatric population.

    Science.gov (United States)

    Atikan, Basak Yildiz; Cavusoglu, Cengiz; Dortkardesler, Merve; Sozeri, Betul

    2016-02-01

    Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early. PMID:25515621

  20. T-cell activation is an immune correlate of risk in BCG vaccinated infants.

    Science.gov (United States)

    Fletcher, Helen A; Snowden, Margaret A; Landry, Bernard; Rida, Wasima; Satti, Iman; Harris, Stephanie A; Matsumiya, Magali; Tanner, Rachel; O'Shea, Matthew K; Dheenadhayalan, Veerabadran; Bogardus, Leah; Stockdale, Lisa; Marsay, Leanne; Chomka, Agnieszka; Harrington-Kandt, Rachel; Manjaly-Thomas, Zita-Rose; Naranbhai, Vivek; Stylianou, Elena; Darboe, Fatoumatta; Penn-Nicholson, Adam; Nemes, Elisa; Hatheril, Mark; Hussey, Gregory; Mahomed, Hassan; Tameris, Michele; McClain, J Bruce; Evans, Thomas G; Hanekom, Willem A; Scriba, Thomas J; McShane, Helen

    2016-01-01

    Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR(+) CD4(+) T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR(+) CD4(+) T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations. PMID:27068708

  1. Frequency of positive tuberculin skin test in bcg-vaccinated asymptomatic adults in pakistan

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of positive tuberculin skin test (TST) in BCG-vaccinated asymptomatic healthy Pakistani adults. Study Design: Cross sectional study. Place and Duration of Study: The study was carried out in Military Hospital, Rawalpindi in 2008 over six months. Patients and Methods: One hundred and thirty six individuals fulfilling inclusion and exclusion criteria of study were recruited after consent. They were subjected to TST (Mantoux test) and results were interpreted after 72 hours of injection. Test was recorded as positive if the indurated area was > 10 mm, and strongly positive if > 15 mm. Results: All participants were male with the mean age of 26.35+-6.164 years. The overall frequency of positive TST was 41.2%. Out of these, 9.6% were strongly positive. Conclusion: In healthy, BCG-vaccinated adult Pakistani population, TST is found to be positive in high frequency, and even induration of more than 15 mm was seen in significant number. In view of low specificity, TST should not be relied upon for the diagnosis of active tuberculosis (TB). (author)

  2. Comparative Study on the Immunogenicity between Recombinant MS-Sj26GST Vaccine and Recombinant BCG-Sj26GST Vaccine in Schistosoma japonicum

    Institute of Scientific and Technical Information of China (English)

    戴五星; 高红; 黄海浪; 袁野; 胡佳杰; 皇甫永穆

    2003-01-01

    The BALB/c mice were immunized with rMS-Sj26GST and rBCG-Sj26GST vaccine inSchistosoma japonicum by subcutaneous injection. After they were immunized for 8 weeks, the eye-balls were removed to get blood and macrophages of abdominal cavity and spleen cells were harves-ted. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating abilityand NO release was used to measure the phagocytic activity of the macrophages. By using ELISAkit, the levels of interleukin-2 (IL-2) and interferon-γ(IFN-γ) in serum and the splenic lymphocyt-ic cultured supernatant were detected. The results showed that after the mice were immunized with106 CFU of rMS-Sj26GST and rBCG-Sj26GST vaccine separately by subcutaneous injection, prolif-erating ability of splenic lymphocytes in the mice showed no difference (P>0.05), but both weresignificantly increased as compared with that in the control group(P<0.05); The contents of NOin the intraperitoneal macrophages of rMS-Sj26GST vaccine group were significantly lower than inthe control group (P<0. 001) and rBCG-Sj26GST vaccine group (P<0. 01); The levels of serumIL-2 in the rMS-Sj26GST vaccine group were significantly increased as compared with that in thecontrol group (P<0. 001), vector group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05);The contents of serum IFN-γ in the rMS-Sj26GST vaccine group were significantly increased ascompared with that in the control group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05).The contents of IFN-γ in the cultured supernatant were significantly lower than those of rBCG-Sj26GST vaccine group (P<0. 001), but were significantly increased as compared with that in thecontrol group (P<0.01). It was indicated that both vaccines could enhance the immune response ofthe mice, but rMS-Sj26GST vaccine had stronger immunogenicity than rBCG-Sj26GST vaccine.

  3. Changes in the resistance of mice to enteral infection and prolonged irradiation induced by live BCG vaccine

    International Nuclear Information System (INIS)

    The influence of the live BCG vaccine on the antiinfection resistance to heterologic stimulus and on the radioresistance at the prolonged irradiation is studied. In the latter case mice have been induced intradermally 0.1 mg. of BCG and in 15 days they have been irradiated by 137Cs γ rays in the 1600 R dose, with 1 R/min. rate. It is concluded that under the influence of vacination by live BCG microbacteria there can occur on a certain stage of the development of immunologic process the natural resistance weakening of the body expressed in our experiments in the decrease of resistance to heterologic infection and prolonged γ ray irradiation effect in two weeks after vaccine induction

  4. 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

  5. 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.

  6. Local skin reaction following an accidental injection from a BCG vaccine in a healthcare worker

    Directory of Open Access Journals (Sweden)

    Kundan Mittal

    2011-02-01

    Full Text Available Exposure to blood-borne pathogens from sharp injuriescontinue to pose a significant risk to healthcare workers(HCW. The number of sharps injuries sustained by HCW is stillunclear, primarily due to under-reporting of events.Healthcare professionals are at risk of sustaining such injuriesfrom hollow-bore needles. Sharps injuries are associated withrisk of infection with blood-borne pathogens such as humanimmunodeficiency virus (HIV, hepatitis B virus (HBV hepatitisC virus (HCV and other live organisms. Here we are reportinga case of an adverse reaction in a HCW due to an accidentalsharps injury by a needle used to administer the BacillusCalmittee Gurien (BCG vaccine.

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

    OpenAIRE

    Dean, GS; Clifford, D.; Whelan, AO; Tchilian, EZ; Beverley, PCL; Salguero, FJ; Z. Xing; Vordermeier, HM; Villarreal-Ramos, B

    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...

  8. Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.

    Science.gov (United States)

    Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos

    2016-03-01

    Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis. PMID:26494773

  9. Concomitant administration of Mycobacterium bovis BCG with the meningococcal C conjugate vaccine to neonatal mice enhances antibody response and protective efficacy.

    Science.gov (United States)

    Brynjolfsson, Siggeir F; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-11-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM(197), in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM(197). BCG was administered concomitantly, a day or a week before MenC-CRM(197). An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM(197), with increased IgG response (P = 0.002) and SBA (8-fold) after a second immunization with MenC-CRM(197) without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM(197) together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM(197) alone (P = 0.0015). Sixteen days after the second immunization with MenC-CRM(197), increased IgG (P CRM(197) plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth. PMID:21900528

  10. 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 M.

    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.

  11. 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.

  12. 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

  13. Natural variation in immune responses to neonatal Mycobacterium bovis Bacillus Calmette-Guerin (BCG Vaccination in a Cohort of Gambian infants.

    Directory of Open Access Journals (Sweden)

    Chris Finan

    Full Text Available BACKGROUND: There is a need for new vaccines for tuberculosis (TB that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-gamma is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN-gamma responses to BCG in this age group are poorly described. Characterisation of IFN-gamma responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. METHODOLOGY/PRINCIPAL FINDINGS: 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-gamma, interleukin (IL-5 and IL-13 responses to purified protein derivative (PPD, killed Mycobacterium tuberculosis (KMTB, M. tuberculosis short term culture filtrate (STCF and M. bovis BCG antigen 85 complex (Ag85 were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen made IFN-gamma responses and there was significant correlation between IFN-gamma responses to the different mycobacterial antigens (Spearman's coefficient ranged from 0.340 to 0.675, p = 10(-6-10(-22. IL-13 and IL-5 responses were generally low and there were more non-responders (33-75% for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens CONCLUSIONS/SIGNIFICANCE: Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine

  14. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zhou Xing

    Full Text Available BACKGROUND: Recombinant adenovirus-vectored (Ad tuberculosis (TB vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. METHODS AND FINDINGS: Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n, AdAg85A intramuscularly (i.m, BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb. At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. CONCLUSIONS: Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

  15. Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

    Science.gov (United States)

    Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

    2015-12-01

    Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. PMID:26577130

  16. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  17. Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

    Science.gov (United States)

    Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

    2009-07-01

    Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife. PMID:19617486

  18. Oral re-vaccination of Eurasian wild boar with Mycobacterium bovis BCG yields a strong protective response against challenge with a field strain

    OpenAIRE

    Gortázar, Christian; Beltrán-Beck, Beatriz; Joseba M. Garrido; Aranaz, Alicia; Sevilla, Iker A.; Boadella, Mariana; Lyashchenko, Konstantin P; Galindo, Ruth C.; Montoro, Vidal; Domínguez, Lucas; Juste, Ramón; De La Fuente, Jose

    2014-01-01

    Abstract Background Field vaccination trials with Mycobacterium bovis BCG, an attenuated mutant of M. bovis, are ongoing in Spain, where the Eurasian wild boar (Sus scrofa) is regarded as the main driver of animal tuberculosis (TB). The oral baiting strategy consists in deploying vaccine baits twice each summer, in order to gain access to a high proportion of wild boar piglets. The aim of this study was to assess the response of wild boar to re-vaccination with BCG and to subsequent challenge...

  19. BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs.

    Science.gov (United States)

    Kaufmann, Eva; Spohr, Christina; Battenfeld, Sibylle; De Paepe, Diane; Holzhauser, Thomas; Balks, Elisabeth; Homolka, Susanne; Reiling, Norbert; Gilleron, Martine; Bastian, Max

    2016-03-15

    A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis-infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies. PMID:26889044

  20. 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.

  1. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System

    OpenAIRE

    Ting-Yu Angela Liao; Alice Lau; Sunil Joseph; Vesa Hytönen; Zakaria Hmama

    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 deve...

  2. A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG▿ †

    OpenAIRE

    Tullius, Michael V.; Harth, Günter; Masleša-Galić, Saša; Dillon, Barbara J.; Horwitz, Marcus A.

    2008-01-01

    Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to ...

  3. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    Science.gov (United States)

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies. PMID:25144542

  4. Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

    Science.gov (United States)

    Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

    2014-03-01

    There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. PMID:24269321

  5. Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not.

    Science.gov (United States)

    Rook, Graham A W; Dheda, Keertan; Zumla, Alimuddin

    2006-01-01

    New vaccine candidates for tuberculosis are beginning to enter clinical trials. In this review we discuss issues surrounding the design of these candidates, and the way they were screened in animal models. First, screening vaccines for their ability to attenuate inevitably fatal tuberculosis in immunologically naïve mice might be leading to the selection of inappropriate candidates. We need to screen vaccines for their ability to stop the development of progressive disease, since this is what they must achieve in man. A solution to this problem is proposed. Secondly, we point out that some mouse models of tuberculosis in laboratories in developing countries, where exposure to environmental mycobacteria is large, mimic neglected aspects of human disease more closely than do low-dose infections in hyper-susceptible immunologically naïve mice in the USA or Europe. We need to think more about geographical differences in immunological experience, and these mouse models can help us. Thirdly, we conclude that in developing countries where BCG fails this is not because there is too little Th1 response, but rather because the Th1 response is rendered ineffective and immunopathological by other subversive mechanisms, including IL-4 responses and inappropriate regulatory T cell function. Therefore, we suggest that vaccines that will work in those countries might need to have immunoregulatory properties that can switch off pre-existing subversive mechanisms, and block their development in the future. The development of such vaccines, that might work where BCG does not, will require a greater understanding of the roles of the many types of regulatory T cell in tuberculosis. PMID:16510309

  6. Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ji, Ping; Hu, Zhi-Dong; Kang, Han; Yuan, Qin; Ma, Hui; Wen, Han-Li; Wu, Juan; Li, Zhong-Ming; Lowrie, Douglas B; Fan, Xiao-Yong

    2016-02-01

    The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate. PMID:26111521

  7. Successive Intramuscular Boosting with IFN-Alpha Protects Mycobacterium bovis BCG-Vaccinated Mice against M. lepraemurium Infection

    Directory of Open Access Journals (Sweden)

    G. G. Guerrero

    2015-01-01

    Full Text Available Leprosy caused by Mycobacterium leprae primarily affects the skin and peripheral nerves. As a human infectious disease, it is still a significant health and economic burden on developing countries. Although multidrug therapy is reducing the number of active cases to approximately 0.5 million, the number of cases per year is not declining. Therefore, alternative host-directed strategies should be addressed to improve treatment efficacy and outcome. In this work, using murine leprosy as a model, a very similar granulomatous skin lesion to human leprosy, we have found that successive IFN-alpha boosting protects BCG-vaccinated mice against M. lepraemurium infection. No difference in the seric isotype and all IgG subclasses measured, neither in the TH1 nor in the TH2 type cytokine production, was seen. However, an enhanced iNOS/NO production in BCG-vaccinated/i.m. IFN-alpha boosted mice was observed. The data provided in this study suggest a promising use for IFN-alpha boosting as a new prophylactic alternative to be explored in human leprosy by targeting host innate cell response.

  8. BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area?

    Science.gov (United States)

    Daulatabad, Deepashree; Pandhi, Deepika; Singal, Archana

    2016-05-01

    Management of recurrent and or recalcitrant warts can be a therapeutic challenge and in such cases invoking body's own immunity may help to overcome the present episode and also prevent recurrences. Bacilli Calmette Geurin (BCG) immunotherapy has long been considered to be an effective and safe modality in such cases. We present a series of seven cases treated with BCG immunotherapy wherein a single dose of BCG caused regression of wart in 85.7% patients and complete resolution was evident in 28.6% patients. However, the development of adverse effects precluded any further dosages in four of seven (57.1%) patients. This raises serious concern on the safety of this therapeutic modality, especially in a population endemic to tuberculosis. PMID:26809285

  9. Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

    DEFF Research Database (Denmark)

    Diness, B.R.; Roth, A.; Nante, E.; Fisker, A.B.; Lisse, I.M.; Yazdanbakhsh, M.; Whittle, H.; Rodrigues, A.; Aaby, P.; Benn, Christine Stabell

    2008-01-01

    .84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

  10. Fecal volatile organic compound profiles from white-tailed deer (Odocoileus virginianus) as indicators of Mycobacterium bovis exposure or Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccination

    Science.gov (United States)

    White-tailed deer (Odocoileus virginianus) serve as a reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and can be a source of infection in cattle. Vaccination with M. bovis bacille Calmette-Guerin (BCG) is being considered for management of bovine tuberculosis in deer. Presently, no...

  11. Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

    Science.gov (United States)

    Van Bui, T; Lévy-Bruhl, D; Che, D; Antoine, D; Jarlier, V; Robert, J

    2015-01-01

    In France, Bacillus Calmette–Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000–2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000–2005 and 2006–2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children. PMID:25811645

  12. Heaf test results after neonatal BCG.

    OpenAIRE

    Crawshaw, P. A.; Thomson, A H

    1988-01-01

    Heaf testing was carried out on 98 preschool Asian children who had received a BCG vaccination. A strongly positive Heaf reaction (grade 3) occurred in only two children. Heaf testing can still be used in tuberculosis screening after neonatal BCG.

  13. A Mycobacterium bovis BCG-naked DNA prime-boost vaccination strategy induced CD4⁺ and CD8⁺ T-cell response against Mycobacterium tuberculosis immunogens.

    Science.gov (United States)

    Lu, Miao; Xia, Zhi Yang; Bao, Lang

    2014-01-01

    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. PMID:24741595

  14. 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

    vaccination and positivation to the tuberculin test in the two age groups was studied, thus obtaining information about the previous oral BCG vaccination. Likewise, in 575 children under one year of age and 1113 children one to four years of age, a positive relationship between the previous oral administration of BCG and the positivation to the tuberculin test was found. In analyzing the relationship between the number of doses of previous oral BCG administration and the results of the tuberculin test by the Goodman method, it was found that the proportion of children who had taken three or more doses of BCG by oral administration and showed strong reaction to the tuberculin test is significantly greater than that observed for the non-reactors, a fact which does not hold true for the one to four age group. For the children who had taken one or two doses there was no significant statistical difference.

  15. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

    Directory of Open Access Journals (Sweden)

    Meywald-Walter K

    2006-05-01

    Full Text Available Abstract Background BCG-vaccination can confound tuberculin skin test (TST reactions in the diagnosis of latent tuberculosis infection. Methods We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. Results During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8% had received BCG vaccination and 84 (27.2% had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000. For the TST, the positive response rate was 44.3% (137/309, whilst only 31 (10% showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23, and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5. In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68, increasing to 0.68 (95% CI 0.46–0.81, if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. Conclusion The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

  16. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

    Science.gov (United States)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Foss, Kim Thestrup; Thøstesen, Lisbeth Marianne; Pihl, Gitte Thybo; Andersen, Andreas; Kofoed, Poul-Erik; Pryds, Ole; Greisen, Gorm

    2016-01-01

    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 in Denmark. Participants Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA BCG and 2133 randomised (73 premature) to the control group. Interventions BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation. Main outcome measures Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age BCG vs. control, 95% confidence interval; -3.7 to 2.4), p = 0.67, corresponding to an effect size of Cohen’s d = -0.015 (-0.082 to 0.052). The mean difference in ASQ score for premature children at 22 months 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 PMID:27123570

  17. Evaluation of the Immune Response to Interferon Gamma Release Assay and Tuberculin Skin Test Among BCG Vaccinated Children in East of Egypt: A Cross-Sectional Study.

    Science.gov (United States)

    Beshir, Mohamed Refaat; Zidan, Alaa Ebrahim; El-Saadny, Hosam Fathi; Ramadan, Raghdaa Abdelaziz; Karam, Nehad Ahmed; Amin, Ezzat Kamel; Mohamed, Marwa Zakaria; Abdelsamad, Nahla Mohamed

    2016-04-01

    Bacille Calmette-Guérin vaccine (BCG) vaccination is used routinely in most of countries, especially developing one. The efficacy of the BCG vaccination generally decreases with time. The tuberculin skin test (TST) is a most popular diagnostic test for suspicion of tuberculosis (TB) in children till now, but it has many false positives. The interferon-gamma release assay (IGRA) is more specific than TST for detection of childhood TB, as it is more specific to Mycobacterium tuberculosis.Evaluate the interferon gamma response and TST reaction in BCG vaccinated children in east of Egypt.150 children were included in the study aged 1 month to 12 years; the collected data from the children included, full history taking, clinical examination, examination for the presence or absence of BCG scar under direct light. All the children had performed TST, IGRA.TST was done for all studied group reveal 51.3% with size of reaction <5 mm, 39.3% with size of reaction = 5 to 9 mm while 9.3% with size of reaction ≥10 mm. Mean size of reaction was 4.07 mm. Interferon gamma release assay was done for all studied group reveal 5 children (3.3%) with positive test. There was significant difference between the size of TST reaction and age (P < 0.01) with old children were more frequent to show positive reaction. Also, children with age range 1 month to 1 year were frequently have negative IGRA test, while children with age range 4 years to 12 years were frequently have positive test (P < 0.01). There was moderate agreement between IGRA and TST results (Kappa [κ] = 0.475). With high agreement between IGRA and TST results in children with absent BCG scar (κ = 1000).Therefore, Interferon gamma release assays have higher specificity and lower cross-reactions with BCG vaccination and nontuberculous Mycobacteraie than TST. PMID:27124042

  18. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG The predictive value of the standard tuberculin test in BCG-vaccinated children

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.The applicability of tuberculin test in children under five years of age, BCG-vaccinated during their first year of life, is a controversial matter. With a view to clarifying the subject the predictive positive value of the test in a region of high BCG coverage and low prevalence of tuberculous infection was analysed. From the proportion of strong reactors among infants and school-age children, vaccinated and not unvaccinated, the declining rate of BCG induced allergy and the increment rate of naturally acquired tuberculin sensitivity between the first and the seventh years of life were calculated. Those calculations allowed for the estimation of the respective values for the intermediate ages. The numbers of false positives to be expected were calculated by difference. Knowing the sensibility and the especificity (1 - FP of

  19. Characterization of immune response to killed leishmania major promastigotes plus BCG vaccine in Sudanese volunteers: a double-blind placebo controlled study

    International Nuclear Information System (INIS)

    This work was examined whether intradermal immunization of healthy adult Sudanese volunteers with killed leishmania major (KLM) promastigotes plus BCG would induce antigen-specific T cell responses. Only healthy Sudanese volunteers with negative reactivity to leishmania skin test and with ≤20 mm induration of reactivity to purified protein derivative (PPD) were included in the trial. Group (A) (n=3): received a single dose (0.1ml) at a concentration of 10 mg protein of a whole cell component of KLM promastigotes/ml BCG, group (B) (n=12): received as a single dose of viable attenuated BCG alone (0.1 ml) at a concentration of 1 mg protein/ml diluent, group (C) (n=11): received the vaccine diluent only (Placebo) (o.1 ml). Study subjects were tested for their immunological and clinical responses before intervention, . Following vaccination 65% of group (A) subjects converted in their reactivity to leishmanin skin testing,non of the BCG vaccinated subjects converted in leishmanin skin test and only one subject of group (C) became leishmanin positive. Levels of Interferon-gamma (IFN-γ), interleukin-5 (IL-5) and interleukin-10 (IL-10) were measured by a double sandwich enzyme-linked immunosorbent assay (ELISA). A vaccine was considered as a positive responder in terms of cytokine production when the level of the produced cytokine was equal to the 80th percentile of the levels produced by the volunteers in the placebo group. 92% of the group vaccinated with KLM=BCG had circulating T cells. No significant of IL-5 or Il-10 was reported in any of the volunteers in the three group. Levels of antileishmania specific IgG were measured by ELISA in optical densities. Volunteers with mean antibody titre above the cut-off point (mean=3X standard deviation) were considered to have positive scores. Accordingly after vaccination 7.69% one volunteers in group (A) had a positive antibody response corresponding to 0% in the other two groups. No serious side effects were reported

  20. Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Worth Andrew

    2010-07-01

    Full Text Available Abstract Background The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

  1. Co-administration of IL-1+IL-6+TNF-α with Mycobacterium tuberculosis infected macrophages vaccine induces better protective T cell memory than BCG.

    Directory of Open Access Journals (Sweden)

    Vijender Singh

    Full Text Available BCG has been administered globally for more than 75 years, yet tuberculosis (TB continues to kill more than 2 million people annually. Further, BCG protects childhood TB but is quite inefficient in adults. This indicates that BCG fails to induce long-term protection. Hence there is a need to explore alternative vaccination strategies that can stimulate enduring T cell memory response. Dendritic cell based vaccination has attained extensive popularity following their success in various malignancies. In our previous study, we have established a novel and unique vaccination strategy against Mycobacterium tuberculosis (M. tb and Salmonella typhimurium by utilizing infected macrophages (IM. In short-term experiments (30 days, substantial degree of protection was observed. However, remarkable difference was not observed in long-term studies (240 days due to failure of the vaccine to generate long-lasting memory T cells. Hence, in the present study we employed T cell memory augmenting cytokines IL-1+IL-6+TNF-α and IL-7+IL-15 for the induction of the enhancement of long-term protection by the vaccine. We co-administered the M. tb infected macrophages vaccine with IL-1+IL-6+TNF-α (IM-1.6.α and IL-7+IL-15 (IM-7.15. The mice were then rested for a reasonably large period (240 days to study the bona fide T cell memory response before exposing them to aerosolized M. tb. IM-1.6.α but not IM-7.15 significantly improved memory T cell response against M. tb, as evidenced by recall responses of memory T cells, expansion of both central as well as effector memory CD4 and CD8 T cell pools, elicitation of mainly Th1 memory response, reduction in the mycobacterial load and alleviated lung pathology. Importantly, the protection induced by IM-1.6.α was significantly better than BCG. Thus, this study demonstrates that not only antigen-pulsed DCs can be successfully employed as vaccines against cancer and infectious diseases but also macrophages infected with M. tb

  2. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg

    2011-01-01

    A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African...

  3. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either. PMID:19918257

  4. Construction and expression of a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组 BCG-TSOL18疫苗构建及其表达

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 周必英

    2015-01-01

    We constructed a recombinant Bacillus Calmette‐Guerin(BCG)‐TSOL18 vaccine of Taenia solium and observed the expression of the TSOL18 gene in BCG .The TSOL18 gene of Taenia solium was obtained from the recombinant plasmid pGEX‐TSOL18 by digestion method and cloned into Escherichia coli (E .coli)‐mycobacterium shuttle plasmid pMV261 to con‐struct the recombinant plasmid pMV261‐TSOL18 of Taenia solium ,and the recombinant plasmid was identified by restriction enzyme digestion ,PCR and DNA sequencing .Then ,the recombinant plasmid was transformed into BCG by electroporation to construct the recombinant BCG‐TSOL18 vaccine of Taenia solium ,and the vaccine was identified by PCR .The expression of the TSOL18 gene in BCG was identified by SDS‐PAGE and Western blot .The 393 bp TSOL18 gene fragment was successfully obtained by restriction enzyme digestion .Restriction enzyme digestion ,PCR and DNA sequencing suggested that the recombi‐nant plasmid pMV261‐TSOL18 of Taenia solium was successfully constructed .PCR confirmed that the recombinant plasmid pMV261‐TSOL18 of Taenia solium was successfully transformed into BCG ,suggesting that the recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully constructed .SDS‐PAGE showed that the relative molecular mass (Mr) of TSOL18 target protein was approximately 14 .7 kD .Results of western blot showed the TSOL18 target protein could be recognized by rabbit antiserum or cysticercosis swine serum .The recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully con‐structed .The TSOL18 gene of Taeniasolium was successfully expressed in BCG and the expressed TSOL18 recombinant pro‐tein had specific antigenicity .This result would lay a foundation for further study of the vaccine .%目的:构建猪带绦虫重组BCG‐TSOL18疫苗,研究TSOL18基因在BCG中的表达情况。方法通过酶切的方法从重组质粒pGEX‐TSOL18获取猪带绦虫TSOL18基因,将其定向克隆到大肠

  5. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

  6. Pharmaceutical characterization of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine used for the treatment of superficial bladder cancer.

    Science.gov (United States)

    Groves, M J

    1993-06-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, developed in the 1920s as a treatment and prophylactic for tuberculosis, has proved to be a nonspecific stimulant of the immune system and is now the major form of clinical immunotherapy approved for the treatment of superficial bladder cancer in the United States. However, methods for the production and physical characterization of the vaccine have not been significantly developed since Calmette and Guérin first devised their process for attenuating the organism in 1908. When reconstituted with sterile water immediately before use, the vaccine consists of a suspension of cellular fragments and aggregates and a mixture of dead and living cells. The dose is determined by the number of colony-forming units that develop when the vaccine is allowed to grow in a nutrient medium. This measurement of dose and viability is misleading because each cellular aggregate may consist of several hundred individual cells, but only one need be living to give rise to a single visible colony. Viability should therefore be measured on the basis of residual ATP levels. In this report, the mode of action of BCG vaccine against bladder cancer is reviewed, and attention is drawn to some factors that may need to be controlled during manufacturing and subsequent quality assurance procedures. The morphology of the various parts of the complex pleomorphic life cycle of this Mycobacterium species has been investigated, and the vaccine has been physically evaluated to provide a characterization by contemporary methodologies, including measurement of ATP content and particle size distribution of the dispersed mycobacterial aggregates. PMID:8331524

  7. Gene Expression and Cytokine Profile Correlate With Mycobacterial Growth in a Human BCG Challenge Model

    OpenAIRE

    Matsumiya, Magali; Satti, Iman; Chomka, Agnieszka; Harris, Stephanie A.; Stockdale, Lisa; Meyer, Joel; Helen A. Fletcher; McShane, Helen

    2014-01-01

    Background.  Bacillus Calmette-Guerin (BCG) vaccine is the most widely administered vaccine in the world, yet its mechanism of action remains unclear. We hypothesize that certain immune pathways are associated with reduced mycobacterial growth following BCG challenge in human volunteers. Methods.  We used samples from a mycobacterial challenge in which previously BCG-vaccinated or BCG-naive adults in the United Kingdom were challenged intradermally with a standard dose of BCG. Any remaining B...

  8. BCG-itis — case report, review of the literature

    OpenAIRE

    Brzezinski, Piotr

    2013-01-01

    Tuberculosis still remains a huge global health problem. Control of tuberculosis expansionis very difficult. It requires the long-term use of anti-mycobacterial drugs. The BacilleCalmette-Guérin (BCG) vaccination protects against tuberculosis-related meningitis and disseminatedtuberculosis. Although vaccination with BCG is considered safe, adverse regional(BCG-itis) and disseminated (BCG-osis) diseases preferentially occur in the immunocompromisedhost. The infection with human immunodeficienc...

  9. Dynamic observation of immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组BCG-TSOL18疫苗诱导小鼠免疫应答的动态观察

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 江楠; 周泠; 刘晖; 王灵军; 周必英

    2015-01-01

    Objective To dynamically observe humoral and cellular immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium.Methods Totally 80 Kunming mice were divided into 4 groups by using random number table according to body mass, 20 mice in each group: rBCG-TSOL18 intraperitoneal injection group [mice were vaccinated with 5 × 106 colony forming units (CFU) recombinant BCG-TSOL18 vaccine of Taenia solium through intraperitoneal injection], rBCG-TSOL18 intragastric administration group(mice were vaccinated with 4 × 108 CFU recombinant BCG-TSOL18 vaccine of Taenia solium through intragastric administration), BCG control (mice were vaccinated with 5 × 106 CFU BCG through intraperitoneal injection), PBS control (mice were vaccinated with PBS through intraperitoneal injection).Zero, 2, 4, 6 and 8 weeks after immunization, eye blood was collected and serum w as separated.Levels of specific IgG and IgG2a were detected by enzyme linked immunosorbent assay (ELISA).Proliferation level of spleen lymphocytes was detected by CCK-8.Levels of interleukin-2 (IL-2) and IL-4 were determined by ELISA.Results The level of specific IgG in rBCG-TSOL18 intraperitoneal injection group and rBCG-TSOL18 intragastric administration group increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.310 ± 0.022, 0.356 ± 0.026).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.054 ± 0.005, 0.057 ± 0.006, 0.093 ± 0.014, 0.085 ± 0.010), there were statistically significant differences (all P < 0.05).The level of specific IgG2a increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.965 ± 0.031, 1.144 ± 0.049).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.102 ± 0.014, 0.093 ± 0.012, 0.115 ± 0.012, 0.103 ± 0.013), there were statistically significant differences (all P < 0.05).The proliferation level of spleen

  10. The 3H-thymidine incorporation into the DNA of different tissues of the guinea pip after BCG-vaccination and the radiation insultus

    International Nuclear Information System (INIS)

    The radioprotective effects of BCG vaccines have been examined. The 3H-thymidine incorporation into the DNA of different tissues of the guinea-pig after solitary whole-body irradiation by the doses of 160, 400, and 700 R have been used as a parameter for radiation injuries and radioprotection. The specific activity of DNA has been detected by means of liquid scintillation counting and by indirect photomeric determination of the amount at 7 h p.r. It has been revealed that independent of the chosen irradiation dose, there was no significant difference in the rate of DNA synthesis in the duodenal, testicular, bone marrow, liver, and lymphatic ganglion tissues of animals vaccinated 30 days before irradiation insultus and the rate of DNA synthesis in normal animals. Based on medical evidence, effect principles which can be observed on other antigenous radioprotective substances can be excluded this time. The dose effect curve has qualitatively the same features as the curves of cell cultures and synchronized cell systems in mammals. Furthermore, the process of DNA synthesis was observed for 56 days. During this observation period there was no significant difference to be seen in the rate of duodenal, testicular, bone marrow, and liver tissues in vaccinated and in normal animals. Only in lymphatic tissues the synthesis rate of vaccinated animals has shown a significantly more decreasing tendency than that of normal animals. A relation concerning radioprotective substances containing SH-groups and 'short-term' protectors (endotoxines) could be excluded because of medical evidence. It is suggested to carry out further tests with parameters affecting the RES in order to comprehend radioprotection after BCG vaccination. (orig./MG)

  11. Mycobacterium bovis BCG priming induces a strong potentiation of the antibody response induced by recombinant BCG expressing a foreign antigen.

    OpenAIRE

    Gheorghiu, M; Lagranderie, M R; Gicquel, B M; Leclerc, C D

    1994-01-01

    Several recent studies have demonstrated that strong cellular or humoral immune responses can be induced against foreign antigens expressed by recombinant Mycobacterium bovis BCG. It has therefore been suggested that BCG could represent one of the best candidate vectors for live recombinant vaccines. However, a large percentage of the human population has been immunized by BCG, and this priming could modify the immune response to future recombinant BCG vaccines. In the present study, we have ...

  12. Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-04-01

    Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

  13. PCR identification of Mycobacterium bovis BCG.

    OpenAIRE

    Talbot, E. A.; Williams, D L; Frothingham, R

    1997-01-01

    The attenuated bacillus Calmette-Guérin (BCG) vaccine strain is derived from a virulent strain of Mycobacterium bovis. BCG is difficult to differentiate from other strains of M. bovis and other members of the M. tuberculosis complex by conventional methods. Recently, a genomic region designated RD1 was found to be present in all virulent M. bovis and M. tuberculosis strains tested but deleted from all BCG strains tested. With this information, a multiplex PCR method was developed to detect th...

  14. Ultrasonographic features of BCG lymphadenitis

    International Nuclear Information System (INIS)

    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

  15. BCG protects against tuberculosis irrespective of HIV status

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Range, Nyagosya; Praygod, George Amani;

    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...

  16. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Lisse, Ida M; Aaby, Peter;

    2007-01-01

    BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized...... placebo-controlled trial of VAS, we obtained blood from 614 children at 6 wk of age and from 369 mother-infant pairs at 4 mo of age. We assessed vitamin A status on the basis of serum retinol-binding protein (RBP) and measured serum C-reactive protein to monitor for concurrent infections. RESULTS: RBP...... interval (P = 0.009), particularly in girls (P for interaction = 0.01) and in vitamin A recipients (P = 0.01). CONCLUSIONS: Overall, VAS at birth had no effect on vitamin A status. However VAS may temporarily improve vitamin A status in the subgroup of children of noneducated mothers. In vitamin A...

  17. High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

    Directory of Open Access Journals (Sweden)

    Jiang Weimin

    2009-05-01

    Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

  18. Identification of a 25-kilodalton protein of Mycobacterium bovis BCG to distinguish BCG strains from Mycobacterium tuberculosis.

    OpenAIRE

    Kumar, D; Srivastava, B S; N. B. Singh; Srivastava, R.

    1996-01-01

    Mycobacterium bovis BCG vaccine strains were compared with Mycobacterium tuberculosis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 25-kDa protein observed in the BCG strains was absent in M. tuberculosis. Rabbit antibodies specific to the 25-kDa protein uniquely identified this protein in BCG strains but not in M. tuberculosis. It is suggested that the 25-kDa protein and polyclonal antibodies directed against this antigen can be exploited to distinguish BCG strains from M. ...

  19. Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B

    OpenAIRE

    Chun Wang; Ruiling Fu; Xionglin Fan; Chunwei Shi; Jia Lu; Xindong Teng; Lingxia Chen; Kun Tan; Zhenhua Chen

    2012-01-01

    Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG c...

  20. Enhanced protective efficacy against Mycobacterium tuberculosis afforded by BCG prime-DNA boost regimen in an early challenge mouse model is associated with increased splenic interleukin-2-producing CD4 T-cell frequency post-vaccination.

    Science.gov (United States)

    Kang, Han; Yuan, Qin; Ma, Hui; Hu, Zhi-Dong; Han, De-Ping; Wu, Kang; Lowrie, Douglas B; Fan, Xiao-Yong

    2014-12-01

    The development of improved vaccines and vaccination strategies against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. Simple measurement of interferon-γ frequency or production per se does not provide adequate prediction of immune protection. In this study, we examined the relationship between T-cell immune responses and protective efficacy conferred by the heterologous vaccination strategy, bacillus Calmette-Guérin (BCG) prime-Ag85A DNA boost (B/D), in an early challenge mouse model of pulmonary tuberculosis. The results demonstrated that mice vaccinated with the B/D regimen had a significantly reduced bacillary load compared with BCG-vaccinated mice, and the reduction in colony-forming units was associated with decreased pathology and lower levels of inflammatory cytokines in the infected lungs. Further analysis of immunogenicity showed that the superior protection afforded by the B/D regimen was associated with significantly increased frequency of splenic interleukin-2 (IL-2) -producing CD4 T cells and increased IL-2 production when measured as integrated mean fluorescence intensity post-vaccination as well. These data suggest that measurement of elevated frequency of IL-2-producing CD4 T cells or IL-2 production in the spleens of vaccinated mice can predict vaccine efficacy, at least in the B/D strategy, and add to the accumulating body of evidence suggesting that BCG prime-boost strategies may be a useful approach to the control of M. tuberculosis infection. PMID:24965530

  1. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    Science.gov (United States)

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-01

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. PMID:27026148

  2. Vaccination of calves with Mycobacteria bovis Bacilli Calmete Guerin (BCG) induced rapid increase in the proportion of peripheral blood gammadelta T cells.

    Science.gov (United States)

    Buza, Joram; Kiros, Tadele; Zerihun, Adama; Abraham, Isaac; Ameni, Gobena

    2009-08-15

    Changes in the proportion of peripheral blood T cell subsets after subcutaneous inoculation of cattle with Mycobacterium bovis Bacille Calmette-Guerin (BCG) were studied. Calves were injected with approximately 8 x 10(6) BCG bacillus and blood samples collected at weekly intervals for flow-cytometric analyses to determine the proportion of CD4+, CD8+ and gammadelta T cells. In addition, whole blood samples were stimulated in vitro with M. bovis purified protein derivative (PPD) and the secreted IFN-gamma quantified by ELISA. Results showed cellular and cytokine changes which could be categorized into three phases. The first phase occurred within the first 2 weeks after vaccination involving an increase in proportion of WC1+ gammadelta T cells and a concomitant increase in the secretion of IFN-gamma. These two responses peaked at 2 weeks and waned thereafter. The second phase involved an increase in the CD4/CD8 ratio as a result of an increase in the proportion of CD4+ T cells between 4 and 6 weeks. The third phase involved a decrease in the CD4/CD8 ratio due to an increase in the proportion of CD8+ T cells between 8 and 10 weeks. Surprisingly, the IFN-gamma response was associated with changes in the gammadelta rather than the CD4+ or CD8+ T cells, suggesting that this cytokine was secreted by gammadelta-T cells. These results are consistent with the reported ability of gammadelta T cells to act rapidly and bridging the innate and classically adaptive immune responses. PMID:19178951

  3. Enhanced and Enduring Protection against Tuberculosis by Recombinant BCG-Ag85C and Its Association with Modulation of Cytokine Profile in Lung

    OpenAIRE

    Jain, Ruchi; Dey, Bappaditya; Dhar, Neeraj; Rao, Vivek; Singh, Ramandeep; Gupta, Umesh D.; Katoch, V. M.; Ramanathan, V. D.; Tyagi, Anil K.

    2008-01-01

    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 secretor...

  4. Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis

    OpenAIRE

    Castro, António G.; Fraga, Alexandra G.; Fountain, Jeffrey J.; Rangel-Moreno, Javier; Torrado, Egídio; Saraiva, Margarida; Pereira, Daniela Maria Ramos

    2010-01-01

    Infection usually leads to the development of acquired immune responses associated with clearance or control of the infecting organism. However, if not adequately regulated, immune-mediated pathology can result. Tuberculosis is a worldwide threat, and development of an effective vaccine requires that the protective immune response to Mycobacterium tuberculosis (Mtb) be dissected from the pathological immune response. This distinction is particularly important if new vaccines are to be deliver...

  5. Inhibition of the Multiplication of Mycobacterium leprae by Vaccination with a Recombinant M. bovis BCG Strain That Secretes Major Membrane Protein II in Mice ▿

    OpenAIRE

    Maeda, Y; Tamura, T.; M. Matsuoka; Makino, M.

    2009-01-01

    The ability of a recombinant Mycobacterium bovis BCG strain that secretes major membrane protein II (MMP-II) of Mycobacterium leprae (BCG-SM) to confer protection against leprosy was evaluated by use of a mouse footpad model. C57BL/6J mice intradermally inoculated with BCG-SM produced splenic T cells which secreted significant amounts of gamma interferon (IFN-γ) in response to either the recombinant MMP-II, the M. leprae-derived membrane fraction, or the BCG-derived cytosolic fraction in vitr...

  6. The effect of zinc supplementation during pregnancy on immune response to Hib and BCG vaccines in Bangladesh

    NARCIS (Netherlands)

    Osendarp, S.J.M.; Fuchs, G.J.; Raaij, van J.M.A.; Mahmud, H.; Tofail, F.; Black, R.E.; Prabhakar, H.; Santosham, M.

    2006-01-01

    An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during preg

  7. 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

  8. Descendant of daughter Brazilian BCG Moreau substrain in Poland.

    Science.gov (United States)

    Krysztopa-Grzybowska, Katarzyna; Brzezińska, Sylwia; Augustynowicz-Kopeć, Ewa; Polak, Maciej; Augustynowicz, Ewa; Lutyńska, Anna

    2012-08-10

    In this study we assessed the genomic stability of Mycobacterium bovis BCG Moreau seed lots used in Poland for BCG vaccine production since 1955 by pulsed field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD). BCG vaccine lots were more closely related the original lot -M. bovis BCG Rio de Janeiro Moreau compared with seeds used before 1980, which is consistent with seed lot distribution recorded in the archives. We confirmed the presence of RD8, RD2, senX3-regX3, RD14, DU2-I, whiB3, trcR, the second copy of IS6110 inserted in the promoter region of phoP, mutation D322G in phoR, ΔRD1, and ΔfadD26-ppsA in M. bovis BCG Moreau used for BCG production in Poland. However, unlike the Rio de Janeiro parent BCG, the BCG Moreau substrain used in Poland does not harbour a deletion in Rv3887c, a region that is involved in the membrane transport protein that is part of the ESX-2 type VII secretion system. Differences in the distribution of BCG Moreau for its subsequent use for manufacturing influenced the microevolution of BCG Moreau used in Brazil and Poland. PMID:22749596

  9. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    OpenAIRE

    K. M. Figurin

    2014-01-01

    The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  10. Complete Genome Sequence of Mycobacterium bovis Strain BCG-1 (Russia).

    Science.gov (United States)

    Sotnikova, Evgeniya A; Shitikov, Egor A; Malakhova, Maja V; Kostryukova, Elena S; Ilina, Elena N; Atrasheuskaya, Alena V; Ignatyev, Georgy M; Vinokurova, Nataliya V; Gorbachyov, Vyacheslav Y

    2016-01-01

    Mycobacterium bovisBCG (Bacille Calmette-Guérin) is a vaccine strain used for protection against tuberculosis. Here, we announce the complete genome sequence ofM. bovisstrain BCG-1 (Russia). Extensive use of this strain necessitates the study of its genome stability by comparative analysis. PMID:27034492

  11. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    K. M. Figurin

    2014-07-01

    Full Text Available The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  12. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination. PMID:10566613

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

    OpenAIRE

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

    2011-01-01

    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 ...

  14. Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

    OpenAIRE

    Hwang, Shen-An; Kruzel, Marian L.; Actor, Jeffrey K.

    2008-01-01

    The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ab...

  15. Role for Gr-1+ Cells in the Control of High-Dose Mycobacterium bovis Recombinant BCG

    OpenAIRE

    Panas, Michael W.; Letvin, Norman L.

    2014-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attractive target for development as a live vaccine vector delivering transgenic antigens from HIV and other pathogens. Most studies aimed at defining the clearance of BCG have been performed at doses between 102 and 104 CFU. Interestingly, however, recombinant BCG (rBCG) administered at doses of >106 CFU effectively generates antigen-specific T-cell responses and primes for heterologous boost responses. Thus, defining clearance at high...

  16. Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG

    Directory of Open Access Journals (Sweden)

    José William Cornejo Ochoa

    2010-08-01

    Full Text Available

    Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.

    La tuberculosis meníngea (MTB es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

  17. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

    Directory of Open Access Journals (Sweden)

    Shanmugalakshmi Sadagopal

    Full Text Available BACKGROUND: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE: We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  18. A Point Mutation in the mma3 Gene Is Responsible for Impaired Methoxymycolic Acid Production in Mycobacterium bovis BCG Strains Obtained after 1927

    OpenAIRE

    Behr, Marcel A.; Schroeder, Benjamin G.; Brinkman, Jacquelyn N.; Slayden, Richard A.; Barry, Clifton E.

    2000-01-01

    BCG vaccines are substrains of Mycobacterium bovis derived by attenuation in vitro. After the original attenuation (1908 to 1921), BCG strains were maintained by serial propagation in different BCG laboratories (1921 to 1961). As a result, various BCG substrains developed which are now known to differ in a number of genetic and phenotypic properties. However, to date, none of these differences has permitted a direct phenotype-genotype link. Since BCG strains differ in their abilities to synth...

  19. 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.

  20. Post-exposure vaccination with the vaccine candidate Bacillus Calmette-Guérin ΔureC::hly induces superior protection in a mouse model of subclinical tuberculosis.

    Science.gov (United States)

    Gengenbacher, Martin; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Kaufmann, Stefan H E

    2016-05-01

    The tuberculosis vaccine BCG ΔureC::hly is the most advanced BCG replacement candidate in phase II clinical development. Here we assess the protective capacity of the construct administered to mice as homologous prime-boost vaccine prior Mycobacterium tuberculosis infection and as post-exposure vaccine. Multiple immunization did not improve the superior protection of BCG ΔureC::hly over BCG. Animals with subclinical tuberculosis were better protected when vaccinated with BCG ΔureC::hly as compared to BCG. Our findings suggest further consideration of BCG ΔureC::hly as post-exposure vaccine. PMID:26994939

  1. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

    Science.gov (United States)

    Ratliff, T L; Kavoussi, L R; Catalona, W J

    1988-02-01

    Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine. PMID:3276931

  2. Intranasal Mucosal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances the Protection of BCG-Primed Guinea Pigs against Pulmonary Tuberculosis

    OpenAIRE

    Xing, Zhou; McFarland, Christine T.; Sallenave, Jean-Michel; Izzo, Angelo; Wang, Jun; McMURRAY, David N.

    2009-01-01

    Background Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. Methods and Findings Specific pathogen-free guinea pigs were immuniz...

  3. 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

  4. Estudo sobre a evolução do risco de infecção tuberculosa em área com elevada cobertura por BCG The trend in the risk of tuberculous infection in an area with wide coverage with BCG vaccination

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1985-04-01

    Full Text Available A partir da prevalência de infecção tuberculosa em escolares com 7 anos de idade, calculou-se a taxa de redução do risco anual de infecção na cidade de São Paulo (Brasil, entre 1974 e 1982. Nesse período o declínio médio foi de 5% ao ano. Nas 59 escolas municipais pesquisadas não houve correlação entre a cobertura de vacinação BCG e a prevalência de infecção natural em não-vacinados, à idade estudada. A alergia tuberculínica no grupo de crianças vacinadas, que recebeu a vacina em alguma idade anterior entre o 1° e o 6° ano de vida, revelou-se 2,5 vezes mais intensa do que a alergia no grupo de mesma idade (7 anos, não vacinado previamente. Foram feitos comentários quanto à impropriedade do material utilizado com vistas ao cálculo do verdadeiro valor do risco de infecção tuberculosa na área em questão.The estimation of the risk of tuberculous infection from prevalence data obtained at school-age, in 1974 and in 1982, permitted the determination of the relevant trend in the city of S. Paulo, Brazil, between those years. The risk of infection decreased, on average, by 5% annually during the period. There was no evidence of any association between the proportions of vaccinated children and that of infected children among those unvaccinated, in the 59 schools studied. Tuberculin sensitivity in 7 years old school-children, vaccinated with BCG at any age between the 1st and the 6th year of life was 2.5 times more intense than that in unvaccinaetd children of the same age. With regard to the calculation of the true value of the risk of tuberculous infection, commentaries about the unrealiability of the available data were made.

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

    OpenAIRE

    MohammadReza Rafati; Bizhan Kouchaki

    2015-01-01

    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 conseque...

  6. Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cells

    OpenAIRE

    Redelman-Sidi, Gil; Iyer, Gopa; Solit, David; Glickman, Michael S.

    2013-01-01

    Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infectio...

  7. rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

    OpenAIRE

    Gillis, Thomas P.; Tullius, Michael V.; Horwitz, Marcus A.

    2014-01-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine m...

  8. 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

    inhabitants. Participants 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 enrolment. Intervention BCG vaccination or no vaccination (control). Main outcome measure Hazard ratios for mortality. Results 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 enrolment 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...

  9. The future of neonatal BCG.

    Science.gov (United States)

    Odent, Michel R

    2016-06-01

    We hypothesise that neonatal BCG (Bacillus Calmette-Guérin) might be used to adapt to a new phase in the history of human births. Among most mammals, the placenta is not effective at transferring antibodies to the fetus: antibodies are transferred immediately after birth via the colostrum. Among humans (and other mammals with hemochorial placentas) the transplacental transfer of antibodies (namely IgG) is effective. In humans, foetal concentrations of IgG sub-classes approximate to maternal concentrations at 38weeks and continue to increase thereafter. These facts explain inter-species differences regarding the basic needs of neonates. Among most mammals, the early colostrum is, strictly speaking, vital. Among humans, the main questions are about the bacteriological environment in the birthing place and how familiar it is to the mother. Today, most human beings are born in unfamiliar bacteriological environments characterized by a low microbial diversity. The effects of clinical environments may be amplified by the use of antibiotics and birth by caesarean, i.e. by-passing the bacteriologically rich perineal zone. There is already an accumulation of data confirming that the maturation of a balanced Th1/Th2 immune response is affected by the mode of delivery. There is also an accumulation of epidemiological studies detecting risk factors in the perinatal period for health conditions such as type 1 diabetes (and other autoimmune diseases), atopy, autism and obesity. In such a context there are reasons to plan randomized controlled trials with long term follow-up of the effects of BCG given immediately after birth, as a modulator of Th-1/Th-2 responses. A follow-up period in the region of 6-10years would be long enough to evaluate the prevalence of several nosologically well defined diseases. These studies would be ethically acceptable, since BCG is the only infancy vaccine that has been evaluated through randomised controlled trials with long term follow

  10. 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; Joosten, Leo A B; de Jong, Dirk; van der Meer, Jos W M; Benn, Christine Stabell; van Crevel, Reinout; Netea, Mihai 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...... 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...

  11. Immunotherapy with BCG cell wall plus irradiated tumor cells

    International Nuclear Information System (INIS)

    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 105 viable tumor cells on 7 days after inoculation of 103 to 108 irradiated tumor cells. Mice pretreated with 105 or 106 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 106 irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 106 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

  12. 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.

  13. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; 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 or no inter......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...

  14. A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

    OpenAIRE

    Horwitz, Marcus A.; Harth, Guenter

    2003-01-01

    Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, Mycobacterium bovis BCG, is urgently needed. We describe a recombinant BCG vaccine (rBCG30) expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis, the primary causative agent of TB, that affords greater survival after challenge than parental BCG in the highly demanding guinea pig model of pulmonary TB. Animals immunized ...

  15. Mycobacterium bovis Bacille Calmette-Guérin as a Vaccine Vector for Global Infectious Disease Control

    OpenAIRE

    Kazuhiro Matsuo; Yasuhiro Yasutomi

    2011-01-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) is the only available vaccine for tuberculosis (TB). Although this vaccine is effective in controlling infantile TB, BCG-induced protective effects against pulmonary diseases in adults have not been clearly demonstrated. Recombinant BCG (rBCG) technology has been extensively applied to obtain more potent immunogenicity of this vaccine, and several candidate TB vaccines have currently reached human clinical trials. On the other hand, recent pro...

  16. Duas epidemias de tuberculose em crianças menores de três anos de idade, vacinadas com BCG oral, numa creche do município de São Paulo, Brasil Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG in a day-nursery in S. Paulo county, Brazil

    Directory of Open Access Journals (Sweden)

    Roberto Brólio

    1974-09-01

    Full Text Available São descritas duas epidemias de tuberculose em crianças menores de 3 anos de idade vacinadas com BCG oral, ocorridas numa creche para crianças menores de 5 anos de idade, no município de São Paulo, nos anos de 1967 e 1969. Em 1967 havia no estabelecimento 96 crianças, inicialmente não reatoras ao teste tuberculínico padronizado (PPD, Rt-23, 2 UT. Foram encontrados 19 reatores, sendo 12 reatores fortes (63,2% e 7 reatores fracos (36,8% e imagens radiológicas indicativas de anormalidade pulmonar em 15 crianças ou 78,9% dos reatores. Em 1969 havia no estabelecimento mais 62 crianças não reatoras, que foram acompanhadas separadamente em relação ao grupo de 1967, embora convivessem no mesmo ambiente. Foram encontrados 36 reatores à tuberculina, sendo 29 reatores fortes (80,5% e 7 reatores fracos (19,5% e imagens radiológicas indicativas de anormalidade pulmonar em 11 crianças, ou 30,5% dos reatores. Nesse mesmo ano houve viragem tuberculínica em mais 7 crianças pertencentes ao grupo de não reatores de 1967, sendo 5 reatores fortes e 2 reatores fracos. Nas duas epidemias, as viragens tuberculínicas e as alterações radiológicas pulmonares foram constatadas apenas nas crianças menores de 3 anos de idade, em sua maioria vacinadas previamente com 3 doses de BCG oral, com intervalo de uma semana entre uma dose e outra. A fonte de infecção foi um operário que trabalhou no estabelecimento durante aproximadamente dois meses em 1967 e um mês em 1969, nos locais onde eram mantidas as crianças menores de 3 anos de idade. A vacina administrada por esse método não parece ter influenciado nas conversões tuberculínicas e no desenvolvimento de imunidade específica.Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG, in the year of 1967 and 1969, in a day-nursery in S. Paulo borough, are here described. In 1967 there were 96 children in the place, at first non-reactors, to the standard

  17. 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. PMID:26393347

  18. The Study On Construction, Immunogenicity and Protection Against Mycobacterium tuberculosis of mpt64-recombinant BCG Vaccine%mpt64-卡介苗重组疫苗的构建、免疫原性及抗结核作用

    Institute of Scientific and Technical Information of China (English)

    孙颖; 张灵霞; 吴雪琼; 董恩军

    2011-01-01

    It was aimed to construct mpt64-recombinant BCG vaccine to find an improved vaccine to replace BCG and to prevent TB effectively. The gene of MPT64 was amplified by PCR and recombined with shuttle plasmids pYUB295. The recombinant shuttle plasmid was identified by PCR, enzyme digestion and DNA sequencing and then transformed into BCG by electroporation. The antigen-specific antibody levels of mouse immunized with recombinant BCG were evaluated by ELISA and multiplication of mouse lymph-cell was detected by MTS. The protection against M. tuberculosis of recombinant BCG vaccines was tested by their prevention and treatment experiments. PCR, enzyme digestion, DNA sequencing and SDS-PAGE results showed: The mpt64-recombinant BCG was constructed successfully and can express extrinsic MPT64 gene. The immunity experiment showed :extrinsic gene can be expressed in BCG and can stimulate B cell to produce antibody,the antibody level reached the peak after 45 days; The lymph-cells of each group proliferated when stimulated by different antigen,all stimulation index reached 2. The stimulation index of each group had no obviously difference. The prevention experiment of recombinant BCG against M. tuberculosis was indicated: mpt64-recombinant BCG and BCG can extend mean time to death and reduce death rate in 2 month of those mouse, the protection effect of mpt64-recombinant BCG had no difference with BCG. It could be concluded that the mpt64-ecombinant BCG was constructed successfully. The protection effect of mpt64-recombinant BCG had no difference with BCG.%通过基因工程重组技术将结核分枝杆菌保护性抗原MPT64的编码基因与穿梭质粒载体pYUB295重组,采用电穿孔技术将重组质粒导入到卡介苗中,应用聚合酶链反应(PCR)扩增、聚丙烯酰胺凝胶电泳(PAGE)对mpt64-卡介苗重组疫苗鉴定:成功地构建了MPT64基因pYUB295重组质粒,MPT64蛋白在卡介苗中能分泌表达.卡介苗重组疫苗免

  19. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin

    OpenAIRE

    Grode, Leander; Seiler, Peter; Baumann, Sven; Hess, Jürgen; Brinkmann, Volker; Eddine, Ali Nasser; Mann, Peggy; Goosmann, Christian; Bandermann, Silke; Smith, Debbie; Bancroft, Gregory J; Reyrat, Jean-Marc; van Soolingen, Dick; Raupach, Bärbel; Kaufmann, Stefan H.E.

    2005-01-01

    The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes, which was shown to improve protection against Mycobacterium tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG (hly+ rBCG) vaccine was shown to protect significantly better against aerosol infection with M. tuberculosis than did the parental BCG strain. The isogenic, urease C–deficient hly+ rBCG (ΔureC hl...

  20. 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 of...

  1. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    Science.gov (United States)

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required. PMID:27317453

  2. Bacillus Calmette-Guérin-related cold thigh abscess as an unusual cause of thigh swelling in infants following BCG vaccine administration: a case series

    Directory of Open Access Journals (Sweden)

    Al Shaalan Mohammad

    2011-09-01

    Full Text Available Abstract Introduction Thigh swelling in an infant can be a symptom of a simple benign condition or a life-threatening condition. We observed a cluster of thigh swelling episodes in infants in which the cause was Bacillus Calmette-Guérin-related cold thigh abscess. We report this unusual case series to raise awareness about this diagnosis. Case presentations We performed a retrospective review of five infants (four boys and one girl who presented with Bacillus Calmette-Guérin-related left thigh abscess. The swelling was noticed by the parents at a mean period of three months prior to presentation. The ages at presentation were five, five, eight and nine months for the boys, and six months for the girl. All of the patients were healthy Saudi infants, and received the Bacillus Calmette-Guérin vaccine at birth. Clinically, all of the patients were well and did not demonstrate signs of systemic infection. All patients underwent needle aspiration, with subsequent incision and drainage in four of the five cases. The cultures obtained from the abscess fluids were the key to establishing the diagnosis. Only three patients (60% received antituberculosis drugs. Wound healing lasted for a mean period of approximately seven months. Two-year follow-up was unremarkable for all of our patients. Conclusions Technical errors continue to be significant in the development of vaccine-related complications. Bacillus Calmette-Guérin-related cold thigh abscess is an extremely rare entity.

  3. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Directory of Open Access Journals (Sweden)

    Rosamund Chapman

    Full Text Available Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP. Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206] were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]. The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]. Mice primed with 10(7 CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6 splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge.

  4. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Science.gov (United States)

    Chapman, Rosamund; Bourn, William R; Shephard, Enid; Stutz, Helen; Douglass, Nicola; Mgwebi, Thandi; Meyers, Ann; Chin'ombe, Nyasha; Williamson, Anna-Lise

    2014-01-01

    Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG) that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP). Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10(7) CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6) splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge. PMID:25061753

  5. Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection

    OpenAIRE

    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 o...

  6. Ag85A DNA疫苗加强免疫显著提高卡介苗初免小鼠的抗结核T细胞免疫应答%Ag85A DNA vaccination boosting enhances BCG primed-mice anti-tuberculosis T cell responses

    Institute of Scientific and Technical Information of China (English)

    康涵; 范小勇; 袁琴; 吴福明; 沈芳

    2013-01-01

    Objective To construct DNA vaccine expressing Mycobacterium tuberculosis(Mtb) immunodominant antigen Ag85A and analyze its anti-tuberculosis T cell responses in BCG primed-mice after DNA vaccination boosting.Methods The coding gene of Ag85A mature fragment was amplified by PCR with H37Rv genomic DNA as template,and then cloned into the eukaryotic expression vector pVAX1 to construct Ag85A DNA vaccine.After purification,Ag85A DNA vaccine was injected intramuscularly twice in BCG primed-mice with BCG vaccination and DNA vaccination alone as control.Eight weeks post-vaccination,spleen lymphocytes were separated and were then used to analyze Mtb antigen specific effector T cell response and polyfuntional IFN-γ/TNF-α/IL-2 secreting CD4+ T cell frequencies and intensities,and CD8+T cell responses by IFN-γ ELISPOT assay and intracellular staining,respectively.Results Compared to BCG vaccinated-and DNA vaccinated-mice,Ag85A DNA boosting not only enhanced significantly BCG primed-mice IFN-γ+TNF-α+IL-2+,IFN-γ+ IL-2+,TNF-α+IL-2+ and IL-2+ CD4+ T cell frequencies and IL-2 secretion,but also improved significantly IFN-γ-secreting and IL-2-secreting CD8+ T cell frequencies.Condusion Ag85A DNA vaccine was constructed successfully and was demonstrated to enhance significantly BCG primed-mice Mtb antigen specific CD4+ and CD8+ T cell responses when boosting,which is beneficial to improve BCG immunogenicity and its waning immune protection against Mtb.%目的 构建表达结核分枝杆菌(Mycobacterium tuberculosis,Mtb)免疫优势抗原Ag85A的DNA疫苗,分析其加强免疫后提高卡介苗(BCG)初免小鼠的抗结核T细胞免疫应答.方法 以Mtb毒株H37Rv基因组DNA为模板,PCR扩增Ag85A抗原编码的结构基因并克隆至真核表达载体pVAX1中构建其DNA疫苗;接着,将纯化后的该DNA疫苗加强免疫BCG初免小鼠2针,以BCG和DNA单独免疫小鼠为对照,免疫8周后无菌分离脾淋巴细胞,分别应用IFN-γ ELISPOT和多

  7. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    WANG QiuYue; LI JianHua; ZHANG XiChen; LIU ChengWu; CAO LiLi; REN KeYan; GONG PengTao; CAI YaNan

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry in-dustry. Enhanced green fluorescent protein (EGFP) tagged recombinant Bacille Calmette-Guerin (rBCG), as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study. Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response. The colonization of rBCG in liver, spleen, lung, kidney and caecum was observed by laser confocal microscopy. Real-time quantitative RT-PCR showed s rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization. These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  8. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry industry.Enhanced green fluorescent protein(EGFP) tagged recombinant Bacille Calmette-Guerin(rBCG),as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study.Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response.The colonization of rBCG in liver,spleen,lung,kidney and caecum was observed by laser confocal microscopy.Real-time quantitative RT-PCR showed a rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization.These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  9. New tuberculosis vaccines.

    Science.gov (United States)

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  10. Immunological efficacy of Bacille Calmette-Guérin vaccina-tion in Egyptian children:case series

    Institute of Scientific and Technical Information of China (English)

    Malak Shaheen; Ashraf Madkour

    2008-01-01

    Bacille Calmette-Guérin (BCG)vaccine is one of the most widely used vaccines in children.In Egypt,it is a part of the national compulsory childhood immunization program.The most controversial aspect of BCG is the variable efficacy found in different studies.This study was to evaluate the efficacy status of the available BCG vaccine in Egypt within the last 10 years (BCG-Copenhagen).The pilot cross sectional study included 597 Egyptian children randomly selected.Their ages ranged from 6 months to 10 years old (mean_5 years,medi-an:3 years).All were assessed for history of BCG vaccine intake (primary at infancy and /or secondary at school age)and examined for the presence BCG scar.A group of the vaccinated children (62 children with BCG scar and 69 children without BCG scar)were further assessed with tuberculin skin test (TST).Preva-lence of BCG vaccine intake in the studied children was 86.9% (519 /597).Efficacy in term of BCG scar af-ter vaccination was 66.6% (346 /519).However,efficacy in term of post BCG vaccination tuberculin sensiti-zation was only 3.8% (5 /131).BCG vaccination program in Egypt seems to be widely prevalent;however, the immunological efficacy of the available strain is questionable.

  11. The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates

    OpenAIRE

    Prentice, S; Jallow, MW; Prentice, AM; MRC-International Nutrition Group

    2015-01-01

    : Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates from non-tuberculous pathogens, but no biological mechanism to explain such effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial protection via a hepcidin-mediated hypoferraemia, limiting iron availability for pathogens. To test this we conducted a trial in 120 Gambian neonates comparing iron status in the first 5-days of life after allocation to: (1) All routine vaccinations at bir...

  12. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  13. TB vaccine development: where are we and why is it so difficult?

    OpenAIRE

    Wilkie, Morven E M; McShane, Helen

    2014-01-01

    The development of an effective TB vaccine remains paramount to achieving the goal of global eradication of TB by 2050. The only licensed vaccine, BCG, has variable efficacy and is poorly effective in high burden countries. The development of promising candidate vaccines to either ‘boost’ a BCG primed immune system or replace BCG altogether is a key area for innovative research. Here, we discuss some of the issues encountered in the development of potential candidate vaccines and the future c...

  14. Digestive juices action on the absorption and the oral BCG destination

    International Nuclear Information System (INIS)

    The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fall of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, sup(14)C-glycerol. The levels of radioactivity recovered at the first day in the organs of mice receiving either gastric instillation of sup(14)C-BCG, sonically disrupted sup(14)-BCG or sup(14)C glycerol were very similar. Subsequently, sonicated sup(14)C-BCG and sup(14)C-glycerol were involved in a biological decay process, while the level of sup(14)C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping thereafter according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive. (author)

  15. Genetic control of antibody responses induced by recombinant Mycobacterium bovis BCG expressing a foreign antigen.

    OpenAIRE

    Lagranderie, M; Lo-Man, R; Dériaud, E; Gicquel, B; Gheorghiu, M; Leclerc, C

    1997-01-01

    Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG infection is under genetic control and could modify the immune responses induced against an antigen delivered by such engineered microorganisms. To investigate this question, we analyzed the immune responses of various...

  16. Factors predicting BCG immunization status in northern Nigeria: a behavioral-ecological perspective.

    Science.gov (United States)

    Babalola, Stella; Lawan, Umar

    2009-03-01

    This study examines the predictors of Bacille Calmette-Guérin (BCG) immunization status among infants in northern Nigeria using a behavioral-ecological model. The findings show only 37.3 percent of the children had received BCG vaccine, and reveal that BCG immunization status in northern Nigeria is influenced by multiple layers of factors, including child's characteristics, parental or household factors, community characteristics, vaccine supply and the policy environment. At the child's level, place of birth and ownership of an immunization card are the two most significant predictors. The parental and household predictors of BCG immunization status include maternal use of antenatal care, maternal knowledge about immunization, maternal exposure to child health information, social influence and paternal approval of immunization. Both the regularity of vaccine supply to the health facility and the state of residence are associated independently with BCG immunization status. These findings stress the need for interventions at multiple levels in order to increase BCG immunization status. PMID:19240190

  17. Novel Human In Vitro System for Evaluating Antimycobacterial Vaccines

    OpenAIRE

    Kampmann, Beate; Tena, Gwen N.; Mzazi, Shumikazi; Eley, Brian; Young, Douglas B.; Levin, Michael

    2004-01-01

    Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existing Mycobacterium bovis BCG “gold standard.” It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with...

  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. Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors.

    Science.gov (United States)

    Hart, Bryan E; Asrican, Rose; Lim, So-Yon; Sixsmith, Jaimie D; Lukose, Regy; Souther, Sommer J R; Rayasam, Swati D G; Saelens, Joseph W; Chen, Ching-Ju; Seay, Sarah A; Berney-Meyer, Linda; Magtanong, Leslie; Vermeul, Kim; Pajanirassa, Priyadharshini; Jimenez, Amanda E; Ng, Tony W; Tobin, David M; Porcelli, Steven A; Larsen, Michelle H; Schmitz, Joern E; Haynes, Barton F; Jacobs, William R; Lee, Sunhee; Frothingham, Richard

    2015-07-01

    The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful generation of recombinant BCG strains possessing consistent insert expression has encountered challenges in stability. Here, we describe a method for the development of large recombinant BCG accession lots which stably express the lentiviral antigens, human immunodeficiency virus (HIV) gp120 and simian immunodeficiency virus (SIV) Gag, using selectable leucine auxotrophic complementation. Successful establishment of vaccine stability stems from stringent quality control criteria which not only screen for highly stable complemented BCG ΔleuCD transformants but also thoroughly characterize postproduction quality. These parameters include consistent production of correctly sized antigen, retention of sequence-pure plasmid DNA, freeze-thaw recovery, enumeration of CFU, and assessment of cellular aggregates. Importantly, these quality assurance procedures were indicative of overall vaccine stability, were predictive for successful antigen expression in subsequent passaging both in vitro and in vivo, and correlated with induction of immune responses in murine models. This study has yielded a quality-controlled BCG ΔleuCD vaccine expressing HIV gp120 that retained stable full-length expression after 10(24)-fold amplification in vitro and following 60 days of growth in mice. A second vaccine lot expressed full-length SIV Gag for >10(68)-fold amplification in vitro and induced potent antigen-specific T cell populations in vaccinated mice. Production of large, well-defined recombinant BCG ΔleuCD lots can allow confidence that vaccine materials for immunogenicity and protection studies are not negatively affected by instability or differences between freshly grown production batches. PMID:25924766

  20. Improvements in the BCG code

    International Nuclear Information System (INIS)

    Some improvements introduced in the BCG code with the objective of making the code faster in execution are reported. The impact of these improvements in terms of CPU time saving is discussed for a sample problem. (author)

  1. Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.

    Science.gov (United States)

    Liang, Jinping; Teng, Xindong; Yuan, Xuefeng; Zhang, Ying; Shi, Chunwei; Yue, Tingting; Zhou, Lei; Li, Jianrong; Fan, Xionglin

    2015-08-01

    Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation. PMID:25974877

  2. Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice.

    Science.gov (United States)

    Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner. PMID:26509812

  3. 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. PMID:27156624

  4. Dose of Incorporated Immunodominant Antigen in Recombinant BCG Impacts Modestly on Th1 Immune Response and Protective Efficiency against Mycobacterium tuberculosis in Mice

    Directory of Open Access Journals (Sweden)

    Hui Ma

    2014-01-01

    Full Text Available One approach for improving BCG efficacy is to utilize BCG as vehicle to develop recombinant BCG (rBCG strains overexpressing Mycobacterium tuberculosis (M. tb antigens. Also expression level of a candidate antigen should impact the final T cell responses conferred by rBCG. In this study, based on our previously constructed differential expression system, we developed two rBCG strains overexpressing M. tb chimeric antigen Ag856A2 (coding a recombinant ag85a with 2 copies of esat-6 inserted at Acc I site of ag85a at differential levels under the control of the subtly modified furA promoters. These two rBCG strains were used to vaccinate C57BL/6 mice and exploit dose of incorporated antigen in rBCG to optimize immune response and protective efficiency against M. tb challenge in mouse model. The results showed that rBCG strains overexpressing Ag856A2 at differential levels induced different antigen-specific IFN-γ production and comparable number of M. tb-specific CD4 T cells expressing IL-2. M. tb challenge experiment showed that rBCG strains afforded enhanced but comparable immune protection characterized by reduced bacillary load, lung pathology, and inflammation. These results suggested that the dose of antigens incorporated in rBCG can impact T cell immune responses but imposed no significantly differential protective efficacies.

  5. BCG (Bacille Calmette-Guerin) Vaccine

    Science.gov (United States)

    ... American Community Summit Background Slideset Children Correctional Facilities Homelessness International Travelers Pregnancy Health Disparities Laboratory Information Model Performance Evaluation Program (MPEP) Drug Susceptibility Testing The Uses of Nucleic Acid Amplification ...

  6. Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

    Science.gov (United States)

    Liu, Jun

    2009-04-01

    Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

  7. 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.

  8. Studies of monocytopoiesis in patients with malignant disease and after imunostimulation with BCG, using 3H-thymidine as a DNA-label

    International Nuclear Information System (INIS)

    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. (orig.)

  9. Rational design of diagnostic and vaccination strategies for tuberculosis

    Directory of Open Access Journals (Sweden)

    Sibele Borsuk

    2012-02-01

    Full Text Available The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092 gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.

  10. Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis

    DEFF Research Database (Denmark)

    Johnson, P D; Stuart, R L; Grayson, M L; Olden, D; Clancy, A; Ravn, P; Andersen, P; Britton, W J; Rothel, J S

    1999-01-01

    QIFN in medical students before and after BCG immunization was assessed, and sensitivity in patients with tuberculosis was assessed. Antigens were PPD derived from M. tuberculosis and two M. tuberculosis-specific proteins, ESAT-6 and MPT-64. Of 60 medical students, all of whom had 0-mm tuberculin skin...... tests (TSTs) at study entry, 58 (97%) were initially classified as negative for M. tuberculosis infection by PPD QIFN. Five months after BCG immunization, 7 of 54 students (13%) had a TST result of >/=10 mm and 11 of 54 students (20%) tested positive by PPD QIFN. ESAT-6- and MPT-64-stimulated IFN......-gamma responses in the medical students were negative prior to and after BCG immunization. For patients with active tuberculosis, 12 of 19 (63%) were positive by PPD QIFN, 11 of 19 (58%) were positive by ESAT-6 QIFN, and 0 of 12 were positive by MPT-64 QIFN. In conclusion, PPD QIFN was negative in 97% of a low...

  11. 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

  12. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  13. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

    OpenAIRE

    Salih Kavukçu; Demet Alaygut; Belde Kasap; Alper Soylu; Gamze Çapakaya; Mehmet Türkmen

    2013-01-01

    Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any) between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 mo...

  14. Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG.

    Science.gov (United States)

    Borsuk, Sibele; Mendum, Tom A; Fagundes, Michel Quevedo; Michelon, Marcelo; Cunha, Cristina Wetzel; McFadden, Johnjoe; Dellagostin, Odir Antônio

    2007-11-01

    Mycobacterium bovis BCG has the potential to be an effective live vector for multivalent vaccines. However, most mycobacterial cloning vectors rely on antibiotic resistance genes as selectable markers, which would be undesirable in any practical vaccine. Here we report the use of auxotrophic complementation as a selectable marker that would be suitable for use in a recombinant vaccine. A BCG auxotrophic for the amino acid leucine was constructed by knocking out the leuD gene by unmarked homologous recombination. Expression of leuD on a plasmid not only allowed complementation, but also acted as a selectable marker. Removal of the kanamycin resistance gene, which remained necessary for plasmid manipulations in Escherichia coli, was accomplished by two different methods: restriction enzyme digestion followed by re-ligation before BCG transformation, or by Cre-loxP in vitro recombination mediated by the bacteriophage P1 Cre Recombinase. Stability of the plasmid was evaluated during in vitro and in vivo growth of the recombinant BCG in comparison to selection by antibiotic resistance. The new system was highly stable even during in vivo growth, as the selective pressure is maintained, whereas the conventional vector was unstable in the absence of selective pressure. This new system will now allow the construction of potential recombinante vaccine strains using stable multicopy plasmid vectors without the inclusion of antibiotic resistance markers. PMID:17888740

  15. 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

    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...

  16. Rapamycin-Induced Enhancement of Vaccine Efficacy in Mice

    OpenAIRE

    Jagannath, Chinnaswamy; Bakhru, Pearl

    2012-01-01

    Th1 immunity protects against tuberculosis infection in mice and humans. The widely used BCG vaccine primes CD4 and CD8 T cells through signaling mechanisms from dendritic cells and macrophages. The latter express MHC-II and MHC-I molecules through which peptides from BCG vaccine are presented to CD4 and CD8 T cells, respectively. Since BCG sequesters within a phagosome that does not fuse with lysosomes, generation of peptides within antigen-presenting cells infected with BCG occurs with redu...

  17. Central Memory CD4+ T Cells Are Responsible for the Recombinant Bacillus Calmette-Guérin ΔureC::hly Vaccine's Superior Protection Against Tuberculosis

    OpenAIRE

    Vogelzang, Alexis; Perdomo, Carolina; Zedler, Ulrike; Kuhlmann, Stefanie; Hurwitz, Robert; Gengenbacher, Martin; Kaufmann, Stefan H.E.

    2014-01-01

    Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4+ T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites fo...

  18. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation.

    Science.gov (United States)

    Caetano, Liliana A; Almeida, António J; Gonçalves, Lídia M D

    2016-01-01

    The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

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

    International Nuclear Information System (INIS)

    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)

  20. Revaccination of cattle with bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

    Science.gov (United States)

    Parlane, Natalie A; Shu, Dairu; Subharat, Supatsak; Wedlock, D Neil; Rehm, Bernd H A; de Lisle, Geoffrey W; Buddle, Bryce M

    2014-01-01

    In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads) displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals) and IFN-γ TB test responses (six of 62 animals) at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with their immune

  1. Estimativa da prevalência de infecção tuberculosa em escolares vacinados com BCG, por meio de método de Bhattacharya The determination of the prevalence of tuberculosis infection among school-children vaccinated by Bhattacharya's method

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1991-04-01

    Full Text Available Em populações muito afetadas por reações tuberculínicas inespecíficas, o teste tuberculínico padronizado, via de regra, superestima a infecção tuberculosa. A bem sucedida aplicação do método de Bhattacharya (método gráfico para a decomposição de uma distribuição de freqüências em componentes normais na análise de resultados do teste em população contaminada por infecçõcs atípicas sugeriu seu uso nos resultados obtidos cm populações vacinadas com BCG. Assim, na análise dos resultados de dois inquéritos tuberculínicos realizados na cidade de São Paulo, SP (Brasil, em 1982 (escolares vacinados entre o segundo e o sexto ano de vida, e em 1988 (escolares vacinados no primeiro ano de vida, foi possível a caracterização e quantificação da componente normal devida à infecção natural em cada uma das misturas. Na população de 1982 o diâmetro médio das reações foi de 17,40 mm com desvio padrão 3,72 mm, e a proporção de infectados foi de 7,71% contra 4,85% nos não vacinados; na população de 1988, o diâmetro médio foi 17,00 mm com desvio padrão 4,67 mm, e a proporção de infectados foi de 4,14% contra 4,48% nos não vacinados. Concluiu-se que o método permite estimar a prevalência da infecção tuberculosa em populações com alta cobertura vacinal, desde que a vacina tenha sido aplicada no primeiro ano de vida.The sucessful application of Bhattacharya's method ( decomposition of frequency distribution into normal components by a grafic method in the analysis of the results of tuberculin test performed on a population sensitized by "anonymous" strains of mycobacteria, suggested the possibility of its application to two samples of BCG vacinated school-children, living in the city of S. Paulo (Brazil. One of the sample groups, vaccinated between the second and seventh years of life, was surveyed in 1982 and the other, vaccinated during the first year of life, was surveyed in 1988. In both populations it

  2. Vaccine development for tuberculosis: current progress

    OpenAIRE

    Orme, Ian M.

    2013-01-01

    Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, BCG, but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have as yet progressed into clinical trials. The leading candidate has advanced to Phase IIb efficacy testing, with disappointing...

  3. PERBANDINGAN PENGGUNAAN MEDIA OGAWA PUSAT PENELITIAN PENYAKIT MENULAR DAN PERUM. BIO FARMA DALAM TES JUMLAH KUMAN VAKSIN BCG DI JAKARTA

    Directory of Open Access Journals (Sweden)

    Dyah W. Isbagio

    2012-09-01

    Full Text Available The aim of the study was to elaborate factors those might have played a role in the interlaboratory results discrepancies of the quality control for BCG vaccine. One hundred and nineteen samples of commercial BCG vaccine, produced by Bio Farma, had been put into extensive viability tests at Communicable Diseases Research Centre. The tests were done in a pair using Ogawa media prepared both by Bio Farma and by Communicable Diseases Research Centre. The Bio Farma's Ogawa medium revealed an average colony-count values of 1,529 x 106 particles/ ml^ while the Communicable Diseases Research Centre's Ogawa medium gave average figure of 1,504 x 10 particles/ml. As judged by student's paired t test, these results were not statistically significant. Apparently, the media used in the test were not responsible for the discrepancies of results of quality control for BCG vaccine.

  4. Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

    Institute of Scientific and Technical Information of China (English)

    Guoqiang Zhang; Lingxia Zhang; Mingcheng Zhang; Linlin Pan; Fengyu Wang; Jun Huang; Guoli Li; Jun Yu; Songnian Hu

    2009-01-01

    Purified protein derivative(PPD)skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tu-berculosis infection and Bacille Calmette-Guerin(BCG)vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames(ORFs)based on the genome sequences of M. tu-berculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coll. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay(ELISA)and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD val-ues for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination(P<0.01). They had at least 92% specificity in healthy controls and six seroantigens(Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A)were never reported with seroantigenicities previously. Thus the approach combining comparative genomies, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

  5. Serial subcultivation of Czechoslovakian and Japanese BCG strains.

    Science.gov (United States)

    Osborn, T W

    1980-10-01

    Changes in the Danish BCG strain under certain regimens of subculture have been shown in preceding studies to be associated with selection of a minority population. Three Czechoslovakian BCG strains, all originally derived from the Danish strain but thereafter and in distinction from it maintained on potato media, have now been investigated. Changes in the immunizing potency of two of these strains have been attributed by other workers to employment of the richer potato media in place of Sauton medium as used for maintenance of the parent Danish strain. However, results from the present study suggest rather that selection of a pre-existing minority genotype or of a new mutant occurred. This proposal is supported by the finding that the third strain has maintained characteristics similar to those of the Danish parent despite many previous transfers on potato media.Another BCG strain investigated was the Japanese which, like the three Czechoslovakian strains, had been previously maintained on potato media. This strain has been shown in the present study to resemble the Danish strain in supporting a minority population yielding non-spreading colonies. Czechoslovakian vaccine prepared with seed culture supplied from Tokyo has retained characteristics similar to those of the Japanese parent. Although a majority population yielding spreading colonies appears so far to have been retained in both centres, it is considered that selection of the minority could still occur in the course of routine transfer. PMID:7005326

  6. 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

    Full Text Available The reversals of Mitsuda's reactions induced by BCG have been objected to based on the possiblem interference of other determination causes of the phenomenon: tuberculous primo-infections, communicants of unsuspected leprosy, revearsals due to other causes, such as anti-diphteric and anti-tetanic vaccination, etc. In order to study the problem, we have used Rhesus monkeys (Macaca mulatta, which were reared in isolation, in an attempt to avoid the referred to interferences. Prior to the experiments, all animals were tested and found negative to radiograph, tuberculin and lepromin tests and were then submitted to the application of BCG vaccine (from 1 to 3 days old, in different doses and by different via. At different times, after the application of BCG, they were again submitted to the radiographic, tuberculin and lepromin tests. In the tables I to IV the experiences were summarised. From the experiments, the following conclusions were reached: 1 - From 12 Rhesus that received BCG 11 showed reversals of the Mitsuda reaction (91.7%. 2 - These reverseals took place both in tests effected shortly after BCG (from 6 days to 2 months, and tests effected much later (from 7 to 12 months after BCG. 3 - Some differences were found in the results, according to the dosis and the application via of the BCG. a - The testicular and peritonela via (0,02g were the only that determined strong positive Mitsuda's reactions (+++. b - By oral via, animals that received high dosis (0.6g and 1.2 g, there resulted uniform and regular reversals, even though of low intensity (+; but from those who got small doses (0.2 g. one showed no reversals in all tests, and the other presented reversals in the 2nd and 3rd tests only, also with low positivity (+. 4 In the 2nd and 3rd Mitsuda's reactions in the same animals, positivity was always precocious (generally within 48 hours, one getting the impression that there occurs a sensibilization of the animal body by the antigen with

  7. 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...

  8. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  9. BCG for carcinoma in situ.

    Science.gov (United States)

    Jakse, G

    1992-01-01

    Bacillus Calmette-Guérin (BCG) is the most effective intravesical therapy of carcinoma in situ of the urinary bladder. Six, weekly instillations of BCG result in a complete remission in about 70-80% of patients. The optimal dose however has still to be defined, and the value of maintenance therapy is also a matter of debate. Recurrent tumours after complete remission occur mainly in the distal ureter and prostatic urethra. In these patients, cystectomy may be required. In about 60-80% of patients, local (e.g. cystitis) and/or systemic (e.g. fever, malaise) side effects are observed. The occurrence of cystitis is associated with the number of instillations, BCG dose and a positive skin test. Systemic side effects are connected with pre-existing dysuria or bacterial cystitis and with traumatic catheterization. Severe toxicity occurs in about 5% of the patients. Prognostic parameters indicating complete remission have yet to be determined, but there is evidence that cytokines detected in the urine and immune-cell infiltration into the bladder wall revealed by immunohistochemistry, can be of value in this respect. PMID:1396945

  10. Low birth weight infants and Calmette-Guérin bacillus vaccination at birth

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Jensen, Henrik; Garly, May-Lill;

    2004-01-01

    In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Guérin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at bir...

  11. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection. PMID:26792673

  12. Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.

    Science.gov (United States)

    Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D

    2005-01-01

    The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A. PMID:15687025

  13. Effect of BCG cell-wall skeleton immunotherapy on the peripheral blood lymphocytes in patients with lung cancer after radiotherapy

    International Nuclear Information System (INIS)

    The effect of radiotherapy on peripheral blood lymphocytes (PBL) of lung cancer and the effect of BCG cell-wall skeleton (BCG-CWS) on recovery of impaired PBL were examined. A remarkable depression of the absolute number of E- or EAC-rosette cells and of the response of PBL to mitogens were observed immediately after radiotherapy, and these continued for several months. With BCG-CWS immunotherapy, the response of PBL to phytohemagglutinin recovered rapidly, compared with non-vaccinated patients. The response of PBL to pokeweed mitogen seemed to give similar results. These results suggested that BCG-CWS injection to the patient receiving radiotherapy was effective for recovery of T-cell response. (author)

  14. [Association between severe tuberculosis in children and previous BCG immunization in a national referral hospital, Peru 1990-2000].

    Science.gov (United States)

    Llanos-Tejada, Félix; del Castillo, Hernán

    2012-03-01

    The objective of the study was to determine the association between BCG immunization and severe tuberculosis (TB). We performed a retrospective study, including medical records from patients of the pneumology department at the National Children's Institute in Peru, between the years 1990-2000. A total of 2106 TB cases were reviewed, from them 259 patients were severe (miliary TB or meningoencephalitic TB). From all, 497 cases did not have history of BCG vaccination, 202 had severe TB and 295 non-severe TB (OR = 0.05, 95% CI = 0.03 to 0.07). In conclusion, children diagnosed with TB and who have been immunized with BCG, has 94% lower risk of developing severe TB, compared to children with TB non-immunized with BCG. PMID:22510912

  15. Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

    Science.gov (United States)

    Scriba, Thomas J; Kaufmann, Stefan H E; Henri Lambert, Paul; Sanicas, Melvin; Martin, Carlos; Neyrolles, Olivier

    2016-09-01

    Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress. PMID:27247343

  16. Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine.

    Science.gov (United States)

    Fletcher, Helen A

    2016-01-01

    Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved vaccine safety but little change in efficacy in animal models. A second-generation recombinant BCG vaccine with an additional deletion of the nuoG gene (BCG ΔureC::hly ΔnuoG) shows improved efficacy in a mouse model compared to that of VPM1002. BCG was first used in humans in 1921 and, like Sleeping Beauty pricked by the spinning wheel, we have slept for 100 years, showing a reluctance to invest in clinical development or in biomanufacturing capacity for TB vaccines. The advance of recombinant BCGs should awaken us from our sleep and call us to invest in new-generation TB vaccines and to protect the biomanufacture of our current BCG vaccine. PMID:27578760

  17. BCG induced granulomatous prostatitis ; a case report

    International Nuclear Information System (INIS)

    Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20

  18. In vitro T-cell profile induced by BCG Moreau in healthy Brazilian volunteers.

    Science.gov (United States)

    Ponte, C; Peres, L; Marinho, S; Lima, J; Siqueira, M; Pedro, T; De Luca, P; Cascabulho, C; Castello-Branco, L R; Antas, P R Z

    2015-01-01

    Tuberculosis (TB) remains the world's leading cause of morbidity and mortality. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine currently in use, its efficacy is highly variable. It has been suggested that early antigenic presentation is a pivotal event leading to a better immune response in TB vaccine models. To investigate this further, we compared in vitro cell-mediated immune responses in the context of early sensitization with TB (i.e. healthy adults vaccinated with BCG when they were young, HD; n = 25) to those in its absence (i.e., newborns with naïve immunity to TB, UV; n = 10) by challenging mononuclear cells with BCG Moreau. After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. In addition, supernatants were assayed for a broad range of cytokines using an array system. The HD group showed robust reactivity to Protein Purified Derivative and BCG while the naïve, UV group did not. Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. Otherwise, only the UV group showed expression of CD25dim+ as an activation marker dependent on BCG infection. In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. Taken together, our results highlight critical roles of early sensitization with TB in mounting cell-mediated immune responses. PMID:25483636

  19. Current status of new tuberculosis vaccine in children.

    Science.gov (United States)

    Pang, Yu; Zhao, Aihua; Cohen, Chad; Kang, Wanli; Lu, Jie; Wang, Guozhi; Zhao, Yanlin; Zheng, Suhua

    2016-04-01

    Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children. PMID:27002369

  20. Current perspective in tuberculosis vaccine development for high TB endemic regions.

    Science.gov (United States)

    Husain, Aliabbas A; Daginawala, Hatim F; Singh, Lokendra; Kashyap, Rajpal S

    2016-05-01

    Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calmette Guerin (BCG) vaccine for more than six decades. In an effort to eradicate TB, vaccinologist around the world have made considerable efforts to develop improved vaccine candidates, based on the understanding of BCG failure in developing world and immune response thought to be protective against TB. The present review represents a current perspective on TB vaccination research, including additional research strategies needed for increasing the efficacy of BCG, and for the development of new effective vaccines for high TB endemic regions. PMID:27156631

  1. The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

    DEFF Research Database (Denmark)

    Andersen, Andreas; Roth, Adam; Jensen, Kristoffer Jarlov;

    2013-01-01

    Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in...

  2. Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

    Directory of Open Access Journals (Sweden)

    Renata Monteiro-Maia

    2014-09-01

    Full Text Available The bacillus Calmette-Guérin (BCG vaccine is the only licensed vaccine for human use against tuberculosis (TB. Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB.

  3. Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

    Science.gov (United States)

    Monteiro-Maia, Renata; Pinho, Rosa Teixeira de

    2014-09-01

    The bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB. PMID:25317714

  4. Prime-boost bacillus Calmette-Guérin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice.

    Science.gov (United States)

    Xu, Ying; Yang, Enzhuo; Wang, Jianguang; Li, Rui; Li, Guanghua; Liu, Guoyuan; Song, Na; Huang, Qi; Kong, Cong; Wang, Honghai

    2014-10-01

    To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guérin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB. PMID:24773322

  5. [Rifampicin-resistant Mycobacterium bovis BCG strain isolated from an infant with NEMO mutation].

    Science.gov (United States)

    Çavuşoğlu, Cengiz; Edeer Karaca, Neslihan; Azarsız, Elif; Ulusoy, Ezgi; Kütükçüler, Necil

    2015-04-01

    It is well known that disseminated Mycobacterium bovis BCG infection is developed after BCG vaccination in infants with congenital cellular immune deficiencies such as mutations in genes along the interleukin (IL)-12/interferon (IFN)-γ pathway and mutations in nuclear factor-kB essential modulator (NEMO). In this report, a rifampicin-resistant M.bovis BCG strain isolated from an infant with NEMO defect was presented. An 8-month-old male infant with NEMO defect admitted to the pediatric outpatient clinic of our hospital with fever, generalized lymphadenopathy and hepatosplenomegaly. Microscopic examination of the smears prepared from lymph node and liver biopsy specimens revealed abundant amount (3+) of acid-fast bacilli (AFB). Rifampicin-susceptible Mycobacterium tuberculosis complex (MTC) was detected by real-time PCR (GeneXpert MTB/RIF; Cepheid, USA) in the samples. The growth of mycobacteria was determined on the 20th day of culture performed in MGIT960 system (Becton Dickinson, USA). The isolate was identified as M.bovis BCG by GenoType MTBC kit (Hain Lifescience, Germany) and defined as M.bovis BCG [SIT 482 (BOV_1)] by spoligotyping. In the primary anti-tuberculosis drug susceptibility test performed by MGIT960 system, the isolate was found susceptible to rifampicin (RIF), isoniazid (INH), streptomycin (STM) and ethambutol (EMB). Then anti-tuberculosis treatment was started to the patient. However, the patient at the age of 2 years, re-admitted to the hospital with the complaint of hepatosplenomegaly. Smear of spontaneously draining abscess material obtained from subcutaneous nodules revealed intensive AFB positivity (3+) once again. In the present instance RIF-resistant MTC was detected with GeneXpert system in the specimen. The growth of mycobacteria was determined on the 13th day of culture and isolate was identified as M.bovis BCG. The present isolate was found susceptible to INH, STM and EMB but resistant to RIF. A mutation in the rpoB gene (codon 531, S

  6. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. (West Virginia Univ. School of Medicine, Morgantown (USA))

    1991-01-01

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

  7. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    International Nuclear Information System (INIS)

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone

  8. Tuberculosis vaccines: beyond bacille Calmette–Guérin

    OpenAIRE

    McShane, Helen

    2011-01-01

    Tuberculosis (TB) disease caused by Mycobacterium tuberculosis (M. tb) remains one of the leading infectious causes of death and disease throughout the world. The only licensed vaccine, Mycobacterium bovis bacille Calmette–Guérin (BCG) confers highly variable protection against pulmonary disease. An effective vaccination regimen would be the most efficient way to control the epidemic. However, BCG does confer consistent and reliable protection against disseminated disease in childhood, and mo...

  9. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

    Directory of Open Access Journals (Sweden)

    Amaya Leunda

    2014-06-01

    Full Text Available Novel efficient vaccines are needed to control tuberculosis (TB, a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine. In this review we provide up to date information on novel tuberculosis (TB vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

  10. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

    Science.gov (United States)

    Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

    2014-01-01

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

  11. [Vaccination for international travelers].

    Science.gov (United States)

    Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

    2016-05-01

    Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. PMID:26920587

  12. Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen

    DEFF Research Database (Denmark)

    Bruffaerts, Nicolas; Pedersen, Lasse Eggers; Vandermeulen, Gaëlle;

    2015-01-01

    two regions with strong predicted SLA-1*0401/SLA-1*0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG...

  13. Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

    Directory of Open Access Journals (Sweden)

    Olusanya Bolajoko O

    2010-01-01

    Full Text Available Abstract Background Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services. Methods A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR was computed for the predictors of delays. Results BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4% were immunised within two weeks and a further 1265 (24.5% by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7% and 6 weeks (20.8%. Conclusions BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of

  14. Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Grandal, Michael V; Poulsen, Christian;

    2010-01-01

    vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4(+) T-cell specific TB10.4 epitope-pattern, which differed completely from...... that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments...... revealed that both TB10.4 and BCG were transported to Lamp(+)-compartments. BCG and TB10.4 however, were directed to different types of Lamp(+)-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely...

  15. Neonatal Bacillus Calmette-Guérin vaccination alleviates lipopolysaccharide-induced neurobehavioral impairments and neuroinflammation in adult mice.

    Science.gov (United States)

    Yang, Junhua; Qi, Fangfang; Yao, Zhibin

    2016-08-01

    The Bacillus Calmette-Guérin (BCG) vaccine is routinely administered to human neonates worldwide. BCG has recently been identified as a neuroprotective immune mediator in several neuropathological conditions, exerting neuroprotection in a mouse model of Parkinson's disease and slowing the progression of clinically isolated syndrome in patients with multiple sclerosis. The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood. However, whether the neonatal BCG vaccination affects the brain in adulthood remains to be elucidated. In the present study, newborn C57BL/6 mice were injected subcutaneously with BCG (105 colony forming units) or phosphate‑buffered saline (PBS). A total of 12 weeks later, the mice were injected intraperitoneally with 330 µg/kg lipopolysaccharide (LPS) or PBS. The present study reported that the neonatal BCG vaccination alleviated sickness, anxiety and depression‑like behavior, lessened the impairments in hippocampal cell proliferation and downregulated the proinflammatory responses in the serum and brain that were induced by the adult LPS challenge. However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood. In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood. PMID:27357155

  16. Immunological evaluation of a component isolated from Mycobacterium bovis BCG with a monoclonal antibody to M. bovis BCG.

    OpenAIRE

    Minden, P; Kelleher, P J; Freed, J. H.; Nielsen, L. D.; Brennan, P J; McPheron, L; McClatchy, J K

    1984-01-01

    A component of Mycobacterium bovis BCG referred to as BCG-a was isolated through the combined use of monoclonal antibody directed to BCG and affinity chromatography. Analysis of BCG-a by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single prominent band with a molecular weight of ca. 10,000. Structural characterization of BCG-a consisting of amino acid composition and amino-terminal sequence determination was carried out. The intact BCG-a antigen was bound by neither t...

  17. Mycobacterium tuberculosis infection and vaccine development.

    Science.gov (United States)

    Tang, Jiansong; Yam, Wing-Cheong; Chen, Zhiwei

    2016-05-01

    Following HIV/AIDS, tuberculosis (TB) continues to be the second most deadly infectious disease in humans. The global TB prevalence has become worse in recent years due to the emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains, as well as co-infection with HIV. Although Bacillus Calmette-Guérin (BCG) vaccine has nearly been used for a century in many countries, it does not protect adult pulmonary tuberculosis and even causes disseminated BCG disease in HIV-positive population. It is impossible to use BCG to eliminate the Mycobacterium tuberculosis (M. tb) infection or to prevent TB onset and reactivation. Consequently, novel vaccines are urgently needed for TB prevention and immunotherapy. In this review, we discuss the TB prevalence, interaction between M. tb and host immune system, as well as recent progress of TB vaccine research and development. PMID:27156616

  18. Animal models of tuberculosis for vaccine development.

    Science.gov (United States)

    Gupta, U D; Katoch, V M

    2009-01-01

    Animal models for testing different vaccine candidates have been developed since a long time for studying tuberculosis. Mice, guinea pigs and rabbits are animals most frequently used. Each model has its own merits for studying human tuberculosis, and none completely mimics the human disease. Different animal models are being used depending upon the availability of the space, trained manpower as well as other resources. Efforts should continue to develop a vaccine which can replace/outperform the presently available vaccine BCG. PMID:19287053

  19. A second-generation anti TB vaccine is long overdue

    Directory of Open Access Journals (Sweden)

    López-Vidal Yolanda

    2004-06-01

    Full Text Available Summary Mycobacterium bovis BCG vaccine significantly reduces the risk of tuberculosis by 50% and continues to be used to prevent tuberculosis around the world. However, it has been shown to be ineffective in some geographical regions. The existence of different BCG strains was described more than 60 years ago, these vary in their antigenic content but the genetic mutations in BCG strains have yet been shown to affect their protection. After the declaration of tuberculosis as a global emergency in 1993, current research attempts to develop a novel more-effective vaccine. Using new technologies, recombinant, auxotroph, DNA, subunit and phylogenetically closely related mycobacteria, naturally or genetically attenuated, have been used as vaccines in animal models, but their protective efficacy, is less than that offered by the current BCG vaccine. Today it is mandatory that a major effort be made to understand how different BCG vaccine strains influence immune response and why in some cases vaccines have failed, so we can rationally develop the next generation of tuberculosis vaccines to reduce the prevalence from 10% to less than 2 % for developed countries.

  20. The Effect of Oral Polio Vaccine at Birth on Infant Mortality

    DEFF Research Database (Denmark)

    Lund, Najaaraq; Andersen, Andreas; Hansen, Anna Sofie K;

    2015-01-01

    7012 healthy normal-birth-weight neonates were randomized to BCG only (intervention group) or OPV0 with BCG (usual practice). All children were to receive OPV with pentavalent vaccine (diphtheria, tetanus, pertussis, Haemophilus influenzae type b, and hepatitis B) at 6, 10, and 14 weeks of age. Seven...

  1. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

    Directory of Open Access Journals (Sweden)

    Salih Kavukçu

    2013-03-01

    Full Text Available Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 months old who had undergone 99mTcDMSAscanning were included in this study. Vertical and horizontaldiameters of BCG scars of the patients in the studygroup were measured. For statistical analysis the greatestdiameter was taken into consideration, and the patientswere divided into 2 subgroups based on the greatest diameterof their BCG scars (Subgroups 1, ≤5 mm, and 2,>5 mm. The patients were also evaluated in 2 groupsas those with (Group 1 or without (Group 2 scars. Bothgroups were compared with subgroups with the largestscar diameters of ≤ 5mm or >5 mmResults: Study population included 108 (82 girls patients.DMSA detected scars in a total of 51 patients.Mean ages of the patients with and without scars were notdifferent (p=0.414. No significant difference was found insize of the BCG scars between renal scar positive andnegative groups (p>0.05.Conclusion: No correlation was found between developmentof renal scar and the size of BCG scar in childrenafter urinary tract infection. J Clin Exp Invest 2013; 4 (1:8-12Key words: BCG scar, renal scar, urinary tract infection,children

  2. Polymorphism in the First Intron of Interferon-Gamma Gene (+874T/A in Patients with BCG Adenitis

    Directory of Open Access Journals (Sweden)

    N Parvaneh

    2009-09-01

    Full Text Available "nBackground: Cytokines and specially interferon-gamma (IFN-g are largely responsible for the regulation of the protective im­mune response against mycobacterial infections. Several studies have clarified the importance of common variants of IFN-g gene regarding the susceptibility to tuberculosis. Bacille Calmette-Guérin (BCG vaccine that is used to prevent se­vere forms of tuberculosis could produce local and systemic side effects. In this study we hypothesized that the IFN-g (+874T/A polymorphism was associated with development of BCG adenitis."nMethods: Thirty patients with BCG adenitis (18 males and 12 females and 30 age and sex-matched healthy children, vacci­nated with BCG during the first two days of life were chosen. All the patients and controls were of Iranian Fars origin and the study was conducted from 2005 to 2007. DNA samples were obtained from 30 patients with BCG adenitis and 30 age and sex matched healthy vaccinees. Polymorphism at +874 was identified using allele specific polymerase chain reac­tion. Allele and genotype frequencies in cases and controls were compared using the χ2 test and odds ratios (OR and their 95% confidence intervals (CI were calculated."nResults: The minor allele (T frequency was significantly lower in patients with BCG adenitis compared to controls (35% vs. 55%, P= 0.02, OR= 0.441, 95% CI= 0.211-0.919. The Armitage trend test revealed a gradually increasing protection from the AA genotype through AT to TT (common odds ratio= 0.49; P= 0.037."nConclusion: Our data suggest that in an Iranian population, the IFN-g (+874T/A polymorphism is associated with develop­ment of BCG adenitis in the vaccinees.

  3. Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

    OpenAIRE

    Jansen, H.M.; The, T H; Orie, N G

    1980-01-01

    Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20...

  4. Influence of Mycobacterium bovis bacillus Calmette-Guérin on antibody and cytokine responses to human neonatal vaccination

    OpenAIRE

    Martin O C Ota; Vekemans, Johan; Schlegel Heueter, Susanna; Fielding, Katherine; Sanneh, Mariama; Kidd, Michael; Newport, Melanie J.; Aaby, Peter; Whittle, Hilton; Lambert, Paul Henri; McAdam, Keith P. W. J.; Siegrist, Claire-Anne; Marchant, Arnaud

    2002-01-01

    The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study gro...

  5. The most massive MaxBCG clusters

    Science.gov (United States)

    Murray, Stephen

    2014-09-01

    Great progress on galaxy clusters has been made in the last several years with SZ and optical surveys. Some new puzzles also emerged and one of them is the mismatch between the stacked Planck SZ fluxes and the model expectations for the MaxBCG clusters. While previous studies regarding this puzzle require the calibration of the true mass and the standard pressure template, we bypass the intermediate steps to directly compare the pressure content derived from the X-ray data with the SZ flux, for massive MaxBCG clusters. This proposal requests Chandra data for 3 clusters to complete a sample of 12 most massive MaxBCG clusters observed with either XMM or Chandra. The results will shed light on the mismatch puzzle and constrain the important scaling relations like Y_X - N_200 and Y_X - Y_SZ.

  6. Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

    OpenAIRE

    Kashangura, Rufaro; Sena, Emily S.; Young, Taryn; Garner, Paul

    2015-01-01

    Background: The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal st...

  7. 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

    . 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 PhD-students or a...... research assistant will call the families and ask them whether they are willing to participate in the study. After the family have made their choice a structured interview with the families will be conducted. Here we ask about the parents’ age, job and dwelling. As a part of the interview, I will use AM O......' 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....

  8. Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guérin▿

    Science.gov (United States)

    Wu, Bo; Huang, Chunhong; Garcia, Lourdes; de Leon, Alfredo Ponce; Osornio, Jose Sifuentes; Bobadilla-del-Valle, Miriam; Ferreira, Leticia; Canizales, Sergio; Small, Peter; Kato-Maeda, Midori; Krensky, Alan M.; Clayberger, Carol

    2007-01-01

    Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis were evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and DBCG-immunized children expressed high levels of cytokines characteristic of an adaptive immune response (gamma interferon, interleukin-2β [IL-12β], and IL-27), while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1α, IL-1β, IL-6, and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways, which may affect long-term vaccine efficacy. PMID:17502394

  9. Unique gene expression profiles in infants vaccinated with different strains of Mycobacterium bovis bacille Calmette-Guerin.

    Science.gov (United States)

    Wu, Bo; Huang, Chunhong; Garcia, Lourdes; Ponce de Leon, Alfredo; Osornio, Jose Sifuentes; Bobadilla-del-Valle, Miriam; Ferreira, Leticia; Canizales, Sergio; Small, Peter; Kato-Maeda, Midori; Krensky, Alan M; Clayberger, Carol

    2007-07-01

    Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis were evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and DBCG-immunized children expressed high levels of cytokines characteristic of an adaptive immune response (gamma interferon, interleukin-2beta [IL-12beta], and IL-27), while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1alpha, IL-1beta, IL-6, and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways, which may affect long-term vaccine efficacy. PMID:17502394

  10. The mc2-CMX vaccine induces an enhanced immune response against Mycobacterium tuberculosis compared to Bacillus Calmette-Guérin but with similar lung inflammatory effects.

    Science.gov (United States)

    Oliveira, Fábio Muniz de; Trentini, Monalisa Martins; Junqueira-Kipnis, Ana Paula; Kipnis, André

    2016-04-01

    Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921, tuberculosis (TB) control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged withMycobacterium tuberculosis (Mtb). The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions. PMID:27074251

  11. The mc2-CMX vaccine induces an enhanced immune response against Mycobacterium tuberculosis compared to Bacillus Calmette-Guérin but with similar lung inflammatory effects

    Directory of Open Access Journals (Sweden)

    Fábio Muniz de Oliveira

    2016-04-01

    Full Text Available Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine has been used since 1921, tuberculosis (TB control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged withMycobacterium tuberculosis (Mtb. The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions.

  12. Revaccination of cattle with bacille Calmette-Guerin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Natalie A Parlane

    Full Text Available In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals and IFN-γ TB test responses (six of 62 animals at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with

  13. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

    OpenAIRE

    Amaya Leunda; Aline Baldo; Martine Goossens; Kris Huygen; Philippe Herman; Marta Romano

    2014-01-01

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already ...

  14. Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

    Science.gov (United States)

    Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

    2016-01-18

    Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation. PMID:26544204

  15. Revaccination of Cattle with Bacille Calmette-Guérin Two Years after First Vaccination when Immunity Has Waned, Boosted Protection against Challenge with Mycobacterium bovis

    OpenAIRE

    Parlane, Natalie A.; Dairu Shu; Supatsak Subharat; D Neil Wedlock; Rehm, Bernd H. A.; Geoffrey W de Lisle; Buddle, Bryce M.

    2014-01-01

    In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the...

  16. Co-Immunization of Plasmid DNA Encoding IL-12 and IL-18 with Bacillus Calmette-Guérin Vaccine against Progressive Tuberculosis

    OpenAIRE

    Jeon, Bo-Young; Eoh, Hyungjin; Ha, Sang-Jun; Bang, Hyeeun; Kim, Seung-Cheol; Sung, Young-Chul; Cho, Sang-Nae

    2011-01-01

    Purpose Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL-12 or IL-18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol cha...

  17. Tuberculosis vaccine: time to look into future.

    Science.gov (United States)

    Chawla, Sumit; Garg, Dinesh; Jain, Ram Bilas; Khanna, Pardeep; Choudhary, Satvinder; Sahoo, Soumya; Singh, Inderjeet

    2014-01-01

    Global burden of tuberculosis is nearly 12 million. As per the WHO Global TB Report 2013, there were an estimated 8.6 million incident cases of TB globally in 2012. Tuberculosis is an issue that affects development through its effect on the health of individuals and families. In humans, neither prior latent infection nor recovery from active TB confers reliable protection against reinfection or reactivation disease. The power of vaccines as a public health intervention lies in their ability to reduce onward transmission of disease as much as in their ability to protect vaccinated individuals; a feature generally referred to as "herd immunity." MVA85A is a booster vaccine, used in con-junction with BCG as part of a prime-boost strategy. BCG serves as the prime vaccination and MVA85A as the boost, operating under the theory that the addition of MVA85A will produce a better immune response and more protection against TB than BCG vaccination alone. There is a critical need to raise the profile of TB vaccine research at the community, national, regional, and global levels in order to generate support and political will, increase investment, create an enabling and supportive environment for clinical trials, and lay the groundwork for acceptance and adoption of new TB vaccines once licensed. PMID:24231233

  18. Rodent malaria: BCG-induced protection and immunosuppression

    International Nuclear Information System (INIS)

    One dose of 107 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 104 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

  19. [Study on recombinant BCG to prevent infections of intracellular pathogens].

    Science.gov (United States)

    Takeshi, Y

    2000-07-01

    Studies on recombinant BCG (rBCG) which my group carried out so far were reviewed. Recombinant BCG which secreted alpha antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. Thus, rBCG secreting merozoite surface protein 1 (MSP1) of Plasmodium yoelii efficiently protected the infection more than recombinant MSP 1 mixed with artificial adjuvant RAS or IFA did. rBCG which secreted excess amounts of antigen 85 complex A inhibited the multiplication of M. leprae in the footpads of mice. rBCG which secreted alpha antigen-fused IL-2 stimulated peritoneal exudate cells of mice resulting in enhancing killing a bladder cancer cell line in vitro. PMID:10979272

  20. Remarks on Boston Consulting Group Method (BCG)

    OpenAIRE

    Jan Mikus; Edward Bieleninik

    2004-01-01

    The situational plan of an enterprise in the market can be determined by means of the BCG method. The analysis consists in graphical presentation of the spatial distribution of the enterprise activity conditions. The presentation is made in two dimensional spaces in which horizontal axis represents the relative participation of the strategic units in the market and vertical axis represents the market growth rate. In such a coordinate system, enterprise activity can be visualized by means of t...

  1. Evolution of cell types and T-cell subsets in the spleens of Mycobacterium bovis BCG-resistant and M. bovis BCG-susceptible strains of mice after infection with M. bovis BCG.

    OpenAIRE

    Denis, M.; Forget, A; Miailhe, A C; Pelletier, M; Skamene, E

    1985-01-01

    In mice, the early host response to intravenous infection with small doses of dispersed Mycobacterium bovis BCG is controlled by the Bcg gene. After infection with a low dose of M. bovis BCG, Lyt-1+ cells were generated in the spleens of BCG-susceptible mice (Bcgs) in parallel with an increase in the proportion of phagocytic cells. Very few changes occurred in the splenic cell types of BCG-resistant mice (Bcgr).

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

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik; Poulsen, Anja; Gustafson, Per; Weise, Christian Frederik; Gomes, Justino; Djana, Queba; Jakobsen, Marianne; Garly, May-Lill; Rodrigues, Amabelia; Aaby, Peter

    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....

  3. Secretion of human interleukin 2 by recombinant Mycobacterium bovis BCG.

    OpenAIRE

    Kong, D.; Kunimoto, D Y

    1995-01-01

    The human interleukin 2 (huIL-2) gene was introduced into Mycobacterium bovis BCG by using the integrative vector pMV306. To express and secrete huIL-2 from BCG, two different plasmids, CI and CII, were made. In CI, the huIL-2-encoding region was under the control of the alpha-antigen promoter of BCG; in CII, the expression of huIL-2 was regulated by the heat shock protein 60 promoter. A signal peptide sequence isolated from the naturally secreted alpha-antigen of BCG was inserted between the...

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

    OpenAIRE

    Lukacs, S.; B. Tschobotko; Szabo, N. A.; Andrew Symes

    2013-01-01

    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 Tra...

  5. Asociación entre tuberculosis infantil grave e inmunización previa con BCG en un hospital de referencia nacional, Perú 1990-2000 Association between severe tuberculosis in children and previous BCG immunization in a national referral Hospital, Peru 1990-2000

    Directory of Open Access Journals (Sweden)

    Félix Llanos-Tejada

    2012-03-01

    Full Text Available El objetivo del estudio fue determinar la asociación entre la inmunización con BCG y tuberculosis grave (TB. Se realizó un estudio retrospectivo, se incluyó fichas de pacientes atendidos en el servicio de neumología del Instituto Nacional de Salud del Niño de Perú, entre los años 1990-2000. Se revisaron un total de 2106 casos de TB entre los que había 259 casos graves (TB miliar o meningoencefalitis por TB. Del total, 497 casos no tenían antecedente de inmunización con BCG; 202 tenían TB grave y 295 TB no grave (OR= 0,05; IC 95%= 0,03-0,07. En conclusión, los niños con diagnóstico de TB y que han sido inmunizados con BCG, tienen 94% menos riesgo de desarrollar TB grave, en comparación a los niños con diagnóstico no inmunizados con BCG.The objective of the study was to determine the association between BCG immunization and severe tuberculosis (TB. We performed a retrospective study, including medical records from patients of the pneumology department at the National Children’s Institute in Peru, between the years 1990-2000. A total of 2106 TB cases were reviewed, from them 259 patients were severe (miliary TB or meningoencephalitic TB. From all, 497 cases did not have history of BCG vaccination, 202 had severe TB and 295 non-severe TB (OR = 0.05, 95% CI = 0.03 to 0.07. In conclusion, children diagnosed with TB and who have been immunized with BCG, has 94% lower risk of developing severe TB, compared to children with TB non-immunized with BCG.

  6. Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Guérin

    DEFF Research Database (Denmark)

    Ravn, P; Boesen, H; Pedersen, B K;

    1997-01-01

    Many aspects of the widely used bacillus Calmette-Guérin (BCG) vaccine against tuberculosis are still the subject of controversy. There is a huge variation in efficacy from one clinical trial to another and no relationship between vaccine-induced skin test conversion and subsequent protection. We...... have studied in vitro cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish donors with different levels of in vitro purified protein derivative (PPD) reactivity before vaccination. The study demonstrated a markedly different development of reactivity to mycobacterial Ags...... depending on the prevaccination sensitivity to PPD. Previously sensitized donors mounted a potent and highly accelerated recall response within the first week of BCG vaccination. Nonsensitized donors, in contrast, exhibited a gradually increasing responsiveness to mycobacterial Ags, reaching maximal levels...

  7. New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters.

    Science.gov (United States)

    Kanno, Alex I; Goulart, Cibelly; Rofatto, Henrique K; Oliveira, Sergio C; Leite, Luciana C C; McFadden, Johnjoe

    2016-04-15

    The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such asMycobacterium bovisBCG orM. smegmatiswas made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinantM. smegmatisbacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in bothM. smegmatisandM. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of theSchistosoma mansoniantigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. PMID:26850295

  8. Comparison of photometric and weight estimation of Mycobacterium content in homogenous BCG cultures containing Tween 80.

    Science.gov (United States)

    Schuh, V; Sír, J; Galliová, J; Svandová, E

    1966-01-01

    A comparison of the weight and photometric methods of primary assay of BCG vaccine has been made, using a vaccine prepared in albumin-free medium but containing Tween 80. In the weight method, the bacteria were trapped on a membrane filter; for photometry a Pulfrich Elpho photometer and an instrument of Czech origin were used. The photometric results were the more precise, provided that the measurements were made within two days of completion of growth; after this time the optical density of the suspension began to decrease slowly. The lack of precision of the weighing method is probably due to the small weight of culture deposit (which was almost on the limit of accuracy of the analytical balance) and to difficulties in the manipulation of the ultrafilter. PMID:5335458

  9. Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users.

    Directory of Open Access Journals (Sweden)

    Léanie Kleynhans

    Full Text Available Most individuals latently infected with Mycobacterium tuberculosis (M.tb contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future.

  10. 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.

  11. Intravesical BCG therapy as cause of miliary pulmonary tuberculosis.

    Science.gov (United States)

    Rosati, Yuri; Fabiani, Andrea; Taccari, Tommaso; Ranaldi, Renzo; Mammana, Gabriele; Tubaldi, Alberto

    2016-03-01

    Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS. PMID:26616461

  12. Drying a tuberculosis vaccine without freezing.

    Science.gov (United States)

    Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R; Edwards, David

    2007-02-20

    With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying. PMID:17299039

  13. A brief history of vaccines & vaccination in India

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya

    2014-01-01

    Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

  14. The Neonatal calf Tuberculosis Vaccine Model: Immune Responses to Protective and Non-protective Vaccines after Aerosol Challenge with Virulent Mycobacterium bovis

    Science.gov (United States)

    An attenuated Mycobacterium tuberculosis delta RD1 knockout and pantothenate auxotroph (mc**2 6030) vaccine failed to protect neonatal calves from a low dose, aerosol M. bovis challenge. In contrast, M. bovis bacille Calmette Guerin (BCG)-vaccinates had reduced tuberculosis-associated pathology as c...

  15. Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau

    DEFF Research Database (Denmark)

    Aaby, Peter; Martins, Cesario; Bale, Carlito;

    2010-01-01

    Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys.......Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys....

  16. Oral Vaccination of Guinea Pigs with a Mycobacterium bovis Bacillus Calmette-Guérin Vaccine in a Lipid Matrix Protects against Aerosol Infection with Virulent M. bovis▿

    OpenAIRE

    Clark, Simon; Cross, Martin L; Nadian, Allan; Vipond, Julia; Court, Pinar; Williams, Ann; Hewinson, R. Glyn; Aldwell, Frank E.; Chambers, Mark A.

    2008-01-01

    Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with Mycobacterium bovis is a cause of considerable economic loss to farmers and the government. The Eurasian badger (Meles meles) represents a wildlife source of recurrent M. bovis infections of cattle in the United Kingdom, and its vaccination against TB with M. bovis bacillus Calmette-Guérin (BCG) is an attractive disease control option. Delivery of BCG in oral bait holds the best prospect for vaccina...

  17. Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combination

    OpenAIRE

    Jinesh G, Goodwin; Kamat, Ashish M

    2012-01-01

    Intravesical bacillus Calmette-Guérin (BCG) immunotherapy results in neutrophil recruitment and subsequent secretion of cytokines to eliminate non-muscle invasive bladder cancer cells. However, bladder cancer cells often resist BCG immunotherapy. Thus, understanding the mechanism of action of BCG, and designing appropriate combination therapies might help to overcome BCG resistance and redirect neutrophils against bladder cancer cells.

  18. Infección diseminada por BCG en la Región de Los Lagos, Chile: Reporte de cinco casos clínicos Disseminated infection by BCG in Región de Los Lagos, Chile: Five cases report

    Directory of Open Access Journals (Sweden)

    ALEXIS STRICKLER P

    2009-01-01

    Full Text Available El bacilo Calmette-Guérin (BCG, es la cepa atenuada de Mycobacterium bovis utilizada en países en vías de desarrollo para la prevención de formas graves de tuberculosis. La vacuna BCG neonatal se administra en países con alta prevalencia de la enfermedad. La mayoría de los vacunados no presenta reacciones adversas, algunos evidencian reacciones secundarias a una inmunidad alterada del huésped. Dichas reacciones varían desde una simple adenomegalia ipsilateral a la inoculación de BCG, hasta una infección diseminada, a menudo mortal. La infección diseminada se ha descrito en pacientes inmuno deficientes secundarios, primarios y en pacientes con defectos genéticos del eje interleuquina 12-23 (IL12/23-interferón gama (IFN-γ denominados "Síndrome de predisposición mendeliana a infecciones micobacterianas" (PMIM. Describimos cinco pacientes con infección por M. bovis-BCG diagnosticados entre 1995-2008, en el Hospital Base de Puerto Montt, Región de Los Lagos, Chile que cumplen con los criterios del PMIM.The bacillus Calmette-Guérin (BCG is the attenuated strain of Mycobacterium bovis used in developing countries for preventing serious forms of tuberculosis. The neonatal BCG vaccine is applied in countries with high prevalence of tuberculosis. Most of the vaccinated individuáis develop no adverse reactions; although, some subjects show side effects due to a host altered immunity. These reactions range from a simple adenomegaly in the same side of BCG vaccine inoculation, to a spread infection, often fatal. A regional or systemic spread has been described in patients with secondary or primary immunodeficiencies and partial or total genetic defects of interleukin IL-12/23 and IFN-γ called as a whole "Mendelian susceptibility to mycobacterial infections" (MSMD. We describe five patients infected with M. bovis BCG-diagnosed between 1995-2008, at the base hospital in the city of Puerto Montt, Región de Los Lagos, Chile. These patients

  19. Risk of Inflammatory Bowel Disease following Bacille Calmette-Guérin and Smallpox Vaccination

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie; Jess, Tine; Sørup, Signe; Ravn, Henrik; Sturegård, Erik; Benn, Christine Stabell; Aaby, Peter; Roth, Adam Anders Edvin

    2013-01-01

    Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark for...

  20. Spinocellulært karcinom opstået ved cikatrice efter Calmette-vaccination

    DEFF Research Database (Denmark)

    Nielsen, Rikke Maria; Andersen, F.; Salskov-Iversen, Maria Luise

    2014-01-01

    Marjolin's ulcer is an aggressive squamous cell carcinoma (SCC) found in chronically inflamed skin. SCC has been reported in smallpox vaccination sites, whereas basal cell carcinomas are more common in scar after bacille Calmette-Guerin (BCG) vaccination. A 72-year-old man presented with a chronic...

  1. Bovine Tuberculosis in Cattle: Vaccines, DIVA Tests, and Host Biomarker Discovery.

    Science.gov (United States)

    Vordermeier, H Martin; Jones, Gareth J; Buddle, Bryce M; Hewinson, R Glyn; Villarreal-Ramos, Bernardo

    2016-02-15

    Bovine tuberculosis remains a major economic and animal welfare concern worldwide. Cattle vaccination is being considered as part of control strategies. This approach, used alongside conventional control policies, also requires the development of vaccine-compatible diagnostic assays to distinguish vaccinated from infected animals (DIVA). We discuss progress made on optimizing the only potentially available vaccine, bacille Calmette Guérin (BCG), and on strategies to improve BCG efficacy. We also describe recent advances in DIVA development based on the detection of host cellular immune responses by blood-testing or skin-testing approaches. Finally, to accelerate vaccine development, definition of host biomarkers that provide meaningful stage-gating criteria to select vaccine candidates for further testing is highly desirable. Some progress has also been made in this area of research, and we summarize studies that defined either markers predicting vaccine success or markers that correlate with disease stage or severity. PMID:26884103

  2. Poliovirus Vaccines

    OpenAIRE

    Isik Yalcin

    2008-01-01

    The two types of poliovirus vaccines are inactivated vaccine, given parenterally, and live virus vaccine, given orally. Oral poliovirus is the vaccine of choice for global eradication. Either inactivated vaccine or oral vaccine may be given concurrently with other routinely recommended childhood vaccines. No serious adverse events have been associated with the vaccine. Oral poliovirus vaccine can cause vaccine associated paralytic poliomyelitis.

  3. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma

    International Nuclear Information System (INIS)

    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

  4. Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice.

    Directory of Open Access Journals (Sweden)

    Kristin L Griffiths

    Full Text Available Interleukin (IL-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4(+ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.

  5. Vaccine Safety

    Science.gov (United States)

    ... the safety of Tdap, Meningococcal, and HPV vaccines Human Papillomavirus (HPV) Vaccine is Very Safe Read about the safety of ... Hepatitis A Vaccine Safety Hepatitis B Vaccine Safety Human Papillomavirus (HPV) Vaccine Safety FAQs about HPV Safety Influenza (Flu) Vaccine ...

  6. The Abell 85 BCG: a nucleated, core-less galaxy

    CERN Document Server

    Madrid, Juan P

    2016-01-01

    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 towards 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 Sersic model.

  7. The Abell 85 BCG: A Nucleated, Coreless Galaxy

    Science.gov (United States)

    Madrid, Juan P.; Donzelli, Carlos J.

    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.

  8. 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

    2010-03-01

    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. PMID:20074686

  9. Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

    OpenAIRE

    Cox, J H; Knight, B. C.; Ivanyi, J.

    1989-01-01

    The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4...

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

    International Nuclear Information System (INIS)

    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. Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine Stabell;

    2015-01-01

    BACKGROUND: We examined the potential sex-differential and non-specific effects of bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) in a rural area of Senegal. METHODS: The 4133 children born in the area between 1996 and 1999 were included in the study...

  12. Vaccination of dogs with six different candidate leishmaniasis vaccines composed of a chimerical recombinant protein containing ribosomal and histone protein epitopes in combination with different adjuvants.

    Science.gov (United States)

    Poot, J; Janssen, L H M; van Kasteren-Westerneng, T J; van der Heijden-Liefkens, K H A; Schijns, V E J C; Heckeroth, A

    2009-07-16

    Chimerical protein "Q", composed of antigenic ribosomal and histone sequences, in combination with live BCG is a promising canine leishmaniasis vaccine candidate; one of the few vaccine candidates that have been tested successfully in dogs. Unfortunately, live BCG is not an appropriate adjuvant for commercial application due to safety problems in dogs. In order to find a safe adjuvant with similar efficacy to live BCG, muramyl dipeptide, aluminium hydroxide, Matrix C and killed Propionibacterium acnes in combination with either E. coli- or baculovirus-produced recombinant JPCM5_Q protein were tested. Groups of five or seven dogs were vaccinated with six different adjuvant-antigen combinations and challenged with a high dose intravenous injection of Leishmania infantum JPC strain promastigotes. All candidate vaccines proved to be safe, and both humoral and cellular responses to the recombinant proteins were detected at the end of the prime-boost vaccination scheme. However, clinical and parasitological data obtained during the 10 month follow-up period indicated that protection was not induced by either of the six candidate vaccines. Although no direct evidence was obtained, our data suggest that live BCG may have a significant protective effect against challenge with L. infantum in dogs. PMID:19500553

  13. 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.

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

    Science.gov (United States)

    Lukacs, S; Tschobotko, B; Szabo, N A; Symes, Andrew

    2013-01-01

    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. PMID:23844314

  15. Status of vaccine research and development of vaccines for tuberculosis.

    Science.gov (United States)

    Evans, Thomas G; Schrager, Lew; Thole, Jelle

    2016-06-01

    TB is now the single pathogen that causes the greatest mortality in the world, at over 1.6 million deaths each year. The widely used the 90 year old BCG vaccine appears to have minimal impact on the worldwide incidence despite some efficacy in infants. Novel vaccine development has accelerated in the past 15 years, with 15 candidates entering human trials; two vaccines are now in large-scale efficacy studies. Modeling by three groups has consistently shown that mass vaccination that includes activity in the latently infected population, especially adolescents and young adults, will likely have the largest impact on new disease transmission. At present the field requires better validated animal models, better understanding of a correlate of immunity, new cost-effective approaches to Proof of Concept trials, and increased appreciation by the public health and scientific community for the size of the problem and the need for a vaccine. Such a vaccine is likely to also play a role in the era of increasing antibiotic resistance. Ongoing efforts and studies are working to implement these needs over the next 5 years, which will lead to an understanding that will increase the likelihood of a successful TB vaccine. PMID:26973073

  16. Potential Benefits of Cattle Vaccination as a Supplementary Control for Bovine Tuberculosis

    OpenAIRE

    Conlan, Andrew J. K.; Ellen Brooks Pollock; McKinley, Trevelyan J.; Andrew P Mitchell; Jones, Gareth J.; Martin Vordermeier; Wood, James L. N.

    2015-01-01

    Vaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Guérin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduc...

  17. Evaluation of attractant flavours for use in oral vaccine baits for badgers ()

    OpenAIRE

    Kelly, David J.; Leigh A. L. Corner; Gormley, Eamonn; Murphy, Denise; Costello, Eamon; Aldwell, Frank E.; Marples, Nicola M.

    2011-01-01

    Abstract European badgers (Meles meles) are a wildlife reservoir for Mycobacterium bovis infection (tuberculosis) in Ireland and the UK and are implicated in the transmission of infection to livestock. Vaccination of badgers with the human BCG vaccine (Bacille Calmette Guerin) is considered as an important strategy to reduce the burden of disease in this species, and a pragmatic approach is likely to involve oral vaccination. In this study, we evaluated nine different flavours for ...

  18. Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau

    DEFF Research Database (Denmark)

    Aaby, Peter; Martins, Cesario; Bale, Carlito;

    2010-01-01

    Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys....

  19. Determining the persistence of Mycobacterium bovis bacille Calmette-Guerin Danish in select tissues of orally vaccinated feral swine (Sus scrofa ssp.).

    Science.gov (United States)

    Nol, Pauline; Robbe-Austerman, Suelee; Rhyan, Jack C; McCollum, Matt P; Triantis, Joni M; Beltrán-Beck, Beatriz; Salman, Mo D

    2016-02-01

    Mycobacterium bovis bacille Calmette-Guerin (BCG) is being considered for vaccination of feral swine (Sus scrofa ssp.). Since BCG is a live bacterium, evaluation of its safety and persistence in tissues is important. Fifteen feral swine received approximately 4.5 × 10(6) colony forming units of BCG Danish via oral bait. Four animals received bait without BCG. At 1, 3, 6, and 9 months post-vaccination, four vaccinates were euthanized. Non-vaccinates were euthanized at 9 months. Clinical signs were not noted in vaccinated pigs at any time. Tissues from all 20 pigs were culture-negative for mycobacteria. Based on our data, BCG is safe and appears not to persist in feral swine tissues after one month post-oral vaccination. However, further work must be performed at higher doses, and on a larger number of animals representing the target population, and further evaluation of persistence in tissues within the first month post-vaccination is needed. PMID:26850536

  20. Vaccine development for Tuberculosis: Past, Present and Future Challenges

    Directory of Open Access Journals (Sweden)

    Dileep Tiwari

    2011-06-01

    Full Text Available About one third of the world's population is infected with Mycobacterium tuberculosis (M. tb, and new infections occur at a rate of about one per second. Additionally, more people in the developed world contact tuberculosis (TB because their immune systems are more likely to be compromised due to higher exposure to immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe, still the treatment is difficult and requires long courses of multiple antibiotics. However, antibiotic resistance is a growing problem in multidrugresistant (MDR tuberculosis. But mostly the prevention relies on screening programs and vaccination, usually with Bacillus Calmette- Guérin (BCG vaccine. BCG is the most commonly used vaccine worldwide, but not as a powerful vaccine. BCG also provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB which accounts for most of the disease burden worldwide. Currently, there is an urgent need for novel, more effective vaccine that can prevent all forms of TB including drug resistant strains for all age groups and among people with HIV. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in year 2004, but, still no effective vaccine is available in a market. Study showed that DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice and it is quite effective against TB. A very promising TB vaccine, MVA85A, is currently in phase II trials and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles making them preferable for areas where HIV is very common and few of

  1. Delivery systems for intradermal vaccination.

    Science.gov (United States)

    Kim, Y C; Jarrahian, C; Zehrung, D; Mitragotri, S; Prausnitz, M R

    2012-01-01

    Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development. PMID:21472533

  2. Differential Immune Responses and Protective Effects in Avirulent Mycobacterial Strains Vaccinated BALB/c Mice.

    Science.gov (United States)

    Liu, Laicheng; Fu, Ruiling; Yuan, Xuefeng; Shi, Chunwei; Wang, Shuling; Lu, Xianyu; Ma, Zhao; Zhang, Xiaoming; Qin, Weiyan; Fan, Xionglin

    2015-07-01

    Screening live mycobacterial vaccine candidates is the important strategy to develop new vaccines against adult tuberculosis (TB). In this study, the immunogenicity and protective efficacy of several avirulent mycobacterial strains including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial, and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our results demonstrated that differential immune responses were induced in different mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae immunization resulted in Th1-type responses in the lung, as well as splenocytes secreting IFN-γ against a highly conserved mycobacterial antigen Ag85A. M. smegmatis also induced the same splenocytes secreting IFN-γ as BCG and M. terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly increased expression of IL-10 and TGF-β in the lung. Most importantly, mice vaccinated with H37Ra and M. vaccae could provide the same protection in the lung against virulent M. tuberculosis challenge as BCG. The result may have important implications in developing adult TB vaccine. PMID:25995039

  3. [Public laboratories for vaccine production: a new paradigm].

    Science.gov (United States)

    Homma, A; di Fabio, J L; de Quadros, C

    1998-10-01

    In Latin America and the Caribbean, public laboratories that produce vaccines have contributed in varying degrees to the control and eradication of vaccine-preventable diseases, and several of them are manufacturing vaccines that are routinely applied in national immunization programs, such as the vaccine against tuberculosis (made with the bacillus of Calmette-Guérin, BCG), the triple vaccine against diphtheriatetanus-pertussis (DTP), tetanus toxoid (TT), the vaccine against measles and the oral vaccine against polio. Thanks to recent scientific strides, one can foresee an important increase in the number of safe and effective vaccines that will be available in the near future for use in routine vaccination programs. However, there are high costs involved in developing such vaccines and in protecting the intellectual property rights involved, and few laboratories in Latin America have the technical capacity to research and develop these vaccines. Such factors will affect the speed with which they are assimilated into vaccination programs in countries of the Region. Currently, public laboratories that manufacture vaccines in the Region are not equipped to compete in this new scenario and run the risk of being completely outmarketed. Thus, they must radically change their style of management and their scientific and technical capabilities, backed by a commitment from governments to improve and strengthen those political and financial aspects that can assure that national laboratories participate in the sustainable supply of vaccines to immunization programs, as well as in researching, developing, and producing new vaccines. PMID:9924504

  4. Ultraviolet susceptibility of BCG and virulent tubercle bacilli

    International Nuclear Information System (INIS)

    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

  5. Oral vaccination of guinea pigs with a Mycobacterium bovis bacillus Calmette-Guerin vaccine in a lipid matrix protects against aerosol infection with virulent M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Nadian, Allan; Vipond, Julia; Court, Pinar; Williams, Ann; Hewinson, R Glyn; Aldwell, Frank E; Chambers, Mark A

    2008-08-01

    Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with Mycobacterium bovis is a cause of considerable economic loss to farmers and the government. The Eurasian badger (Meles meles) represents a wildlife source of recurrent M. bovis infections of cattle in the United Kingdom, and its vaccination against TB with M. bovis bacillus Calmette-Guérin (BCG) is an attractive disease control option. Delivery of BCG in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. Using a guinea pig pulmonary challenge model, we evaluated the protective efficacy of candidate badger oral vaccines, based on broth-grown or ball-milled BCG, delivered either as aqueous suspensions or formulated in two lipids with differing fatty acid profiles (one being animal derived and the other being vegetable derived). Protection was determined in terms of increasing body weight after aerosol challenge with virulent M. bovis, reduced dissemination of M. bovis to the spleen, and, in the case of one oral formulation, restricted growth of M. bovis in the lungs. Only oral BCG formulated in lipid gave significant protection. These data point to the potential of the BCG-lipid formulation for further development as a tool for controlling tuberculosis in badgers. PMID:18519560

  6. Harnessing the beneficial heterologous effects of vaccination.

    Science.gov (United States)

    Goodridge, Helen S; Ahmed, S Sohail; Curtis, Nigel; Kollmann, Tobias R; Levy, Ofer; Netea, Mihai G; Pollard, Andrew J; van Crevel, Reinout; Wilson, Christopher B

    2016-06-01

    Clinical evidence strongly suggests that certain live vaccines, in particular bacille Calmette-Guérin (BCG) and measles vaccines, can reduce all-cause mortality, most probably through protection against non-targeted pathogens in addition to the targeted pathogen. The underlying mechanisms are currently unknown. We discuss how heterologous lymphocyte activation and innate immune memory could promote protection beyond the intended target pathogen and consider how vaccinologists could leverage heterologous immunity to improve outcomes in vulnerable populations, in particular the very young and the elderly. PMID:27157064

  7. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

    OpenAIRE

    Tobiume, Makoto; Shinohara, Tsutomu; Kuno, Takahira; Mukai, Shinji; Naruse, Keishi; Hatakeyama, Nobuo; OGUSHI, FUMITAKA

    2014-01-01

    Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no aci...

  8. Mucosal vaccination against tuberculosis using Ag85A-loaded immunostimulating complexes.

    Science.gov (United States)

    Pabreja, Swati; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-03-01

    Tuberculosis (TB) is one of the major devastating diseases in the world, mainly caused by Mycobacterium tuberculosis. Furthermore, multi-drug resistant TB and extremely drug resistant TB are becoming big problems globally. Bacillus Calmette-Guerin (BCG) is the only available vaccine which provides protection against TB. The BCG vaccine is effective in children but not recommended in adults and elderly patients due to an associated low risk of infection with Mycobacterium tuberculosis and variable effectiveness of the vaccine. The main aim of this research study is to develop such a vaccine which will provide a better and safer profile in children and adults, as well as in elderly patients. In this present study, we prepared pulmonary tubercular vaccine by using an Antigen 85 complex (Ag85)-loaded nanocarrier such as the immunostimulating complex (ISCOM). Immunological outcomes clearly indicated significant improvement in humoral as well as cellular immune responses after pulmonary immunization with ISCOMs containing Quil A in mice. PMID:25307269

  9. Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination

    Directory of Open Access Journals (Sweden)

    de Souza Wayner V

    2007-02-01

    Full Text Available Abstract Background In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. Methods A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. Results The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. Conclusion In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias.

  10. Recommendations for pediatric tuberculosis vaccination in Italy.

    Science.gov (United States)

    Montagnani, Carlotta; Esposito, Susanna; Galli, Luisa; Chiappini, Elena; Principi, Nicola; de Martino, Maurizio

    2016-03-01

    Bacillus Calmette-Guérin (BCG) vaccine is still the only vaccine approved for the prevention of tuberculosis (TB), and is widely used in highly endemic countries, where all newborns receive a single intradermal dose immediately after birth; however, the recommendations concerning its use in Europe vary widely from country to country. This document describes the recommendations of a group of Italian scientific societies concerning its pediatric use in Italy, the persistence of the protection it provides, its safety, its interference with tuberculin skin test (TST) responses, and the children who should be vaccinated. The experts conclude that BCG vaccination provides a good level of protection against tuberculous meningitis and disseminated forms, and a fair level of protection against pulmonary disease; the protective effective lasts at least 10 years, and revaccination offers no advantages over a single administration. The vaccine is safe in immunocompetent subjects, and affects the response to a TST for at least 6 y On the basis of these observations, we recommend its use in Italy in all TST-negative immunocompetent newborns and breastfeeding infants aged <6 months, and all TST-negative children aged between 6 months and 5 y who come from highly epidemic areas, or whose parents come from highly endemic areas, or who have been in contact with a family member with active TB without contracting the disease themselves. PMID:26587764

  11. Protection of Mice with a Divalent Tuberculosis DNA Vaccine Encoding Antigens Ag85B and MPT64

    Institute of Scientific and Technical Information of China (English)

    Xia TIAN; Hong CAI; Yu-Xian ZHU

    2004-01-01

    DNA vaccine may be a promising tool for controlling tuberculosis development. However,vaccines encoding single antigens of mycobacterium did not produce protective effect as BCG did. In the present study, we evaluated the immunogenicity and protective efficacy of a divalent DNA vaccine encoding two immunodominant antigens Ag85B and MPT64 of Mycobacterium tuberculosis. We found that both humoral and Th1-type (high IFN-γ, low IL-4) cellular responses obtained from the divalent DNA vaccine group were significantly higher than that conferred by BCG. RT-PCR results showed that antigens were expressed differentially in various organs in divalent DNA vaccine group. The survival rate for mice treated with the divalent DNA vaccine after challenging with high doses of virulent M. tuberculosis H37Rv was significantly higher than that of the BCG group or any of the single DNA vaccine group. Significant differences were also found between the single and divalent DNA vaccinated mice in terms of body, spleen and lung weight. Bacterial loading decreased about 2000-fold in lungs and about 100-fold in spleens of divalent DNA vaccinated mice when compared with that of the control group. We conclude that our divalent DNA vaccine may be a better choice for controlling tuberculosis disease in animals.

  12. Up-date of the BCG code library

    International Nuclear Information System (INIS)

    Procedures for generating an up-date material library for the BCG code were established. A new library was generated by processing ENDF/B-IV data with the 89-1 version of the LINEAR, RECENT and SIGMA1 programs. The effect of library change in the neutron spectrum and effective multiplication factor of a fast reactor cell was analized. During the course of this study, an error was detected in the BCG code. Although localized in a narrow energy range, the discrepancies in neutron spectrum caused by the error were large enough to yield a difference of about 1% in the effective multiplication factor of the test cell. (author)

  13. Comparative genomics of the Mycobacterium signaling architecture and implications for a novel live attenuated Tuberculosis vaccine.

    Science.gov (United States)

    Zhou, Peifu; Xie, Jianping

    2014-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major threat to global public health. A new TB vaccine affording superior immune protection to M. bovis Bacillus Calmette-Guérin (BCG) is imperative. The advantage of a live attenuated vaccine is that it can mimic the bona fide pathogen, elicit immune responses similar to natural infection, and potentially provide more protection than other vaccines. BCG, the only vaccine and a live attenuated vaccine that is the result of cumulative mutations by serial passage of M. bovis, has provided clues for the construction of novel improved vaccines. A strategy is put forward for identifying a new live attenuated TB vaccine generated by cumulative mutation based on M.tb. Given the important role of the M.tb signaling network consisting of a two-component system, eukaryotic-like Ser/Thr protein kinase system and sigma factor system based on comparisons among M.tb H37Rv, M. bovis, and BCG, we have put a premium on this signaling circuit as the starting point for the generation of an attenuated TB vaccine. PMID:24013364

  14. Immunostimulatory Activity of Recombinant Mycobacterium bovis BCG That Secretes Major Membrane Protein II of Mycobacterium leprae

    OpenAIRE

    Makino, Masahiko; Maeda, Yumi; Inagaki, Katsuya

    2006-01-01

    We previously demonstrated that major membrane protein II (MMP-II) is one of the immunodominant antigens (Ags) of Mycobacterium leprae capable of activating T cells through Toll-like receptor 2. Based on the observation that Mycobacterium bovis BCG secreting a 30-kDa protein offered better protection against tuberculosis, we constructed a recombinant BCG strain (BCG-SM) that secretes MMP-II to improve the potency of BCG against leprosy. The secreted MMP-II protein from BCG-SM stimulated monoc...

  15. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

    DEFF Research Database (Denmark)

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

    2012-01-01

    Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

  16. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... Girls ages 11 and 12 should receive the HPV vaccine series: The vaccine is given in three shots ...

  17. ANALISIS MATRIKS BOSTON CONSULTING GROUP (BCG) UNTUK MEMENANGKAN STRATEGI ORGANISASI

    OpenAIRE

    Haryadi Sarjono; Engkos Achmad Kuncoro

    2013-01-01

    Penelitian ini bertujuan untuk mengetahui posisi tingkat pertumbuhan pasar pada perguruan tinggi khususnya Sekolah Tinggi berdasarkan market share, menggunakan matriks BCG. Unit analisis adalah semua perguruan tinggi swasta yang termasuk dalam Kopertis Wilayah III DKI Jakarta, yang terdiri dari Universitas, Sekolah Tinggi, Institut, dan Akademi. Objek analisis adalah jumlah penerimaan mahasiswa baru. Metode pengumpulan data yang dilakukan dalam penulisan ini adalah dengan metode ...

  18. Mechanisms of cell accumulation induced by Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Octávio Menezes-de-Lima-Júnior

    1997-12-01

    Full Text Available Mycobacteria, specially Mycobacterium tuberculosis are among the micro-organisms that are increasing dramatically the number of infections with death, all over the world. A great number of animal experimental models have been proposed to investigate the mechanisms involved in the host response against these intracellular parasites. Studies of airway infection in guinea-pigs and rabbits, as well as, in mice intravenously infected with BCG have made an important contribution to our understanding of the virulence, pathogenesis and the immunology of mycobacterial infections. Although, there are few models to study the mechanisms of the initial inflammatory process induced by the first contact with the Mycobacteria, and the relevance of the acute generation of inflammatory mediators, cytokines and leukocyte infiltration to the development of the mycobacterial infection. In this work we reviewed our results obtained with a model of M. bovis BCG-induced pleurisy in mice, describing the mechanisms involved in the leukocyte influx induced by BCG at 24 hr. Different mechanisms appear to be related with the influx of neutrophils, eosinophils and mononuclear cells and distinct inflammatory mediators, cytokines and adhesion molecules are involved in the BCG-induced cell accumulation.

  19. Progress in Oral Vaccination against Tuberculosis in Its Main Wildlife Reservoir in Iberia, the Eurasian Wild Boar

    Directory of Open Access Journals (Sweden)

    Beatriz Beltrán-Beck

    2012-01-01

    Full Text Available Eurasian wild boar (Sus scrofa is the main wildlife reservoir for tuberculosis (TB in Iberia. This review summarizes the current knowledge on wild boar vaccination including aspects of bait design, delivery and field deployment success; wild boar response to vaccination with Bacillus Calmette-Guérin (BCG and inactivated Mycobacterium bovis; and wild boar vaccination biosafety issues as well as prospects on future research. Oral vaccination with BCG in captive wild boar has shown to be safe with significant levels of protection against challenge with virulent M. bovis. An oral vaccination with a new heat-killed M. bovis vaccine conferred a protection similar to BCG. The study of host-pathogen interactions identified biomarkers of resistance/susceptibility to tuberculosis in wild boar such as complement component 3 (C3 and methylmalonyl coenzyme A mutase (MUT that were used for vaccine development. Finally, specific delivery systems were developed for bait-containing vaccines to target different age groups. Ongoing research includes laboratory experiments combining live and heat-killed vaccines and the first field trial for TB control in wild boar.

  20. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

    DEFF Research Database (Denmark)

    Villumsen, Marie; Sørup, Signe; Jess, Tine;

    2009-01-01

    Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.......Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines....... In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N=2073) of the...

  1. Disseminated Bacillus Calmette-Guérin and Susceptibility to Mycobacterial Infections-Implications on Bacillus Calmette-Guérin Vaccinations.

    Science.gov (United States)

    Lee, Pamela Pw

    2015-08-01

    Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised. PMID:26477962

  2. Human type 5 adenovirus-based tuberculosis vaccine: is the respiratory route of delivery the future?

    Science.gov (United States)

    Smaill, Fiona; Xing, Zhou

    2014-08-01

    Despite progress in managing TB, there were 8.6 million new cases in 2012. To control TB will require a more effective vaccine than BCG, new drugs and better diagnostic tests. Recombinant replication-defective adenoviruses expressing foreign DNA have been studied as vaccines. We developed and evaluated a recombinant replication-deficient human Ad5 vector expressing Ag85A (Ad5Ag85A) as a TB vaccine in animal models and a Phase I human study. Animal models of Ad5Ag85A show markedly improved protection over BCG alone and immunization via the respiratory route provides the best type of protection. In humans, intramuscular vaccination was safe; Ad5Ag85A was immunogenic and stimulated polyfunctional T cell responses, more potently in previously BCG-vaccinated volunteers. Pre-existing Ad5 antibodies did not dampen the response. Given its potency, Ad5-based TB vaccines are well-positioned to be delivered to the respiratory tract, induce local lung immunity to control TB, and inform innovative approaches to new TB vaccination strategies. PMID:24935214

  3. Analysis of the vaccine potential of plasmid DNA encoding nine mycolactone polyketide synthase domains in Mycobacterium ulcerans infected mice.

    Science.gov (United States)

    Roupie, Virginie; Pidot, Sacha J; Einarsdottir, Tobba; Van Den Poel, Christophe; Jurion, Fabienne; Stinear, Timothy P; Huygen, Kris

    2014-01-01

    There is no effective vaccine against Buruli ulcer. In experimental footpad infection of C57BL/6 mice with M. ulcerans, a prime-boost vaccination protocol using plasmid DNA encoding mycolyltransferase Ag85A of M. ulcerans and a homologous protein boost has shown significant, albeit transient protection, comparable to the one induced by M. bovis BCG. The mycolactone toxin is an obvious candidate for a vaccine, but by virtue of its chemical structure, this toxin is not immunogenic in itself. However, antibodies against some of the polyketide synthase domains involved in mycolactone synthesis, were found in Buruli ulcer patients and healthy controls from the same endemic region, suggesting that these domains are indeed immunogenic. Here we have analyzed the vaccine potential of nine polyketide synthase domains using a DNA prime/protein boost strategy. C57BL/6 mice were vaccinated against the following domains: acyl carrier protein 1, 2, and 3, acyltransferase (acetate) 1 and 2, acyltransferase (propionate), enoylreductase, ketoreductase A, and ketosynthase load module. As positive controls, mice were vaccinated with DNA encoding Ag85A or with M. bovis BCG. Strongest antigen specific antibodies could be detected in response to acyltransferase (propionate) and enoylreductase. Antigen-specific Th1 type cytokine responses (IL-2 or IFN-γ) were induced by vaccination against all antigens, and were strongest against acyltransferase (propionate). Finally, vaccination against acyltransferase (propionate) and enoylreductase conferred some protection against challenge with virulent M. ulcerans 1615. However, protection was weaker than the one conferred by vaccination with Ag85A or M. bovis BCG. Combinations of these polyketide synthase domains with the vaccine targeting Ag85A, of which the latter is involved in the integrity of the cell wall of the pathogen, and/or with live attenuated M. bovis BCG or mycolactone negative M. ulcerans may eventually lead to the development of an

  4. Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

    Science.gov (United States)

    Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

    1993-06-15

    It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection. PMID:8509380

  5. Novel adjuvant formulations for delivery of anti-tuberculosis vaccine candidates.

    Science.gov (United States)

    Agger, Else Marie

    2016-07-01

    There is an urgent need for a new and improved vaccine against tuberculosis for controlling this disease that continues to pose a global health threat. The current research strategy is to replace the present BCG vaccine or boost BCG-immunity with subunit vaccines such as viral vectored- or protein-based vaccines. The use of recombinant proteins holds a number of production advantages including ease of scalability, but requires an adjuvant inducing cell-mediated immune responses. A number of promising novel adjuvant formulations have recently been designed and show evidence of induction of cellular immune responses in humans. A common trait of effective TB adjuvants including those already in current clinical testing is a two-component approach combining a delivery system with an appropriate immunomodulator. This review summarizes the status of current TB adjuvant research with a focus on the division of labor between delivery systems and immunomodulators. PMID:26596558

  6. BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Winters, W D; Stogdill, V D; Radwin, H M

    1981-07-01

    Fifty-one patients with confirmed bladder cancer have enrolled in a prospective evaluation of BCG immunotherapy. Following resection of existing tumors, patients were stratified according to tumor grade and number of previous recurrences and randomly assigned to control or BCG treatment groups. Immunotherapy consisted of six weekly administrations of Pasteur strain BCG using 120 mg intravesically and 5 mg percutaneously. Immunotherapy side effects were minimal and no patient required postponement of BCG treatments. Eleven control (46%) compared with five (22%) BCG-treated patients had tumor recurrence (P = 0.078, chi 2). Prolongation of the disease-free interval with BCG treatment was significantly at the P = 0.016 level by Wilcoxon analysis. Four control and two BCG-treated patients had multiple recurrences. Comparing total episodes of recurrence, nineteen of 79 (24%) control and eight of 85 (7%) BCG group cystoscopic examinations revealed tumor (P = 0.006, chi 2). Immunologic correlates of response to immunotherapy were not statistically significant since only five BCG-treated patients had tumor recurrence. However, four of these five patients evidenced impaired LIF response to PPD at the time of tumor recurrence, and impairment of skin test reactivity and BCG humoral antibody response were more commonly seen in this subgroup of patients. PMID:7016300

  7. Added value of use of a purified protein derivative-based enzyme-linked immunosorbent spot assay for patients with Mycobacterium bovis BCG infection after intravesical BCG instillations.

    Science.gov (United States)

    Heemstra, Karen A; Bossink, Ailko W J; Spermon, Roan; Bouwman, John J M; van der Kieft, Robert; Thijsen, Steven F T

    2012-06-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma. PMID:22461529

  8. Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations

    OpenAIRE

    Heemstra, Karen A.; Bossink, Ailko W. J.; Spermon, Roan; Bouwman, John J. M.; van der Kieft, Robert; Thijsen, Steven F. T.

    2012-01-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.

  9. Human biomarkers: can they help us to develop a new tuberculosis vaccine?

    Science.gov (United States)

    Fletcher, Helen A; Dockrell, Hazel M

    2016-06-01

    The most effective intervention for the control of infectious disease is vaccination. The BCG vaccine, the only licensed vaccine for the prevention of tuberculosis (TB) disease, is only partially effective and a new vaccine is urgently needed. Biomarkers can aid the development of new TB vaccines through discovery of immune mechanisms, early assessment of vaccine immunogenicity or vaccine take and identification of those at greatest risk of disease progression for recruitment into smaller, targeted efficacy trials. The ultimate goal, however, remains a biomarker of TB vaccine efficacy that can be used as a surrogate for a TB disease end point and there remains an urgent need for further research in this area. PMID:27203133

  10. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines

    DEFF Research Database (Denmark)

    Blok, Bastiaan A; Arts, Rob J W; van Crevel, Reinout;

    2015-01-01

    An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can...... protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole-microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system....

  11. Inadvertent Intramuscular Administration of High Dose Bacillus Calmette Guerin Vaccine in a Pre-term Infant

    OpenAIRE

    Banu, Asima; Loganathan, Eswari

    2013-01-01

    This case report examined the natural course of reaction after accidental intramuscular administration of high dose Bacille Calmette-Guιrin (BCG) vaccine into the anterolateral aspect of thigh of a pre-term infant as a part of routine vaccination instead of intra-dermal injection into the arm. There is no consensus on the best management of this complication, although in this case healing was prolonged but was spontaneous without anti-tubercular chemotherapy.

  12. Early cellular immune response to a new candidate mycobacterial vaccine antigen in childhood tuberculosis.

    Science.gov (United States)

    Schepers, K; Dirix, V; Mouchet, F; Verscheure, V; Lecher, S; Locht, C; Mascart, F

    2015-02-18

    The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes. PMID:25583385

  13. IMPROVEMENT OF THE RICHNESS ESTIMATES OF maxBCG CLUSTERS

    International Nuclear Information System (INIS)

    Minimizing the scatter between cluster mass and accessible observables is an important goal for cluster cosmology. In this work, we introduce a new matched filter richness estimator, and test its performance using the maxBCG cluster catalog. Our new estimator significantly reduces the variance in the LX -richness relation, from σlnLx2 = (0.86±0.02)2 to σlnLx2 = (0.69±0.02)2. Relative to the maxBCG richness estimate, it also removes the strong redshift dependence of the LX -richness scaling relations, and is significantly more robust to photometric and redshift errors. These improvements are largely due to the better treatment of galaxy color data. We also demonstrate the scatter in the LX -richness relation depends on the aperture used to estimate cluster richness, and introduce a novel approach for optimizing said aperture which can easily be generalized to other mass tracers.

  14. 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. PMID:27158432

  15. 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. PMID:27158432

  16. Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice.

    Science.gov (United States)

    Chen, Zhenhai; Gupta, Tuhina; Xu, Pei; Phan, Shannon; Pickar, Adrian; Yau, Wilson; Karls, Russell K; Quinn, Frederick D; Sakamoto, Kaori; He, Biao

    2015-12-16

    Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette-Guérin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development. PMID:26552000

  17. The Young face of the BCG ESO 400-G43

    International Nuclear Information System (INIS)

    We briefly discuss the results of a multifrequency study of the blue compact galaxy ESO 400-G43. This galaxy, one of the most luminous BCG:s known, is embedded in a massive HI cloud and shows clear signs of a global burst of star formation. There are substantial evidence that this is the first grand star formation epoch in the history of this galaxy

  18. Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice.

    Science.gov (United States)

    Derrick, Steven C; Yabe, Idalia; Morris, Sheldon; Cowley, Siobhan

    2016-07-01

    Earlier studies aimed at defining protective immunity induced by Mycobacterium bovis BCG immunization have largely focused on the induction of antituberculosis CD4(+) and CD8(+) T cell responses. Here we describe a vaccine consisting of a BCGΔmmaA4 deletion mutant formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with d-(+)-trehalose 6,6'-dibehenate (TDB) (DDA/TDB) adjuvant (A4/Adj) that protected TCRδ(-/-) mice depleted of CD4(+), CD8(+), and NK1.1(+) T cells against an aerosol challenge with M. tuberculosis These mice were significantly protected relative to mice immunized with a nonadjuvanted BCGΔmmaA4 (BCG-A4) mutant and nonvaccinated controls at 2 months and 9 months postvaccination. In the absence of all T cells following treatment with anti-Thy1.2 antibody, the immunized mice lost the ability to control the infection. These results indicate that an unconventional T cell population was mediating protection in the absence of CD4(+), CD8(+), NK1.1(+), and TCRγδ T cells and could exhibit memory. Focusing on CD4(-) CD8(-) double-negative (DN) T cells, we found that these cells accumulated in the lungs postchallenge significantly more in A4/Adj-immunized mice and induced significantly greater frequencies of pulmonary gamma interferon (IFN-γ)-producing cells than were seen in the nonvaccinated or nonadjuvanted BCG control groups. Moreover, pulmonary DN T cells from the A4/Adj group exhibited significantly higher IFN-γ integrated median fluorescence intensity (iMFI) values than were seen in the control groups. We also showed that enriched DN T cells from mice immunized with A4/Adj could control mycobacterial growth in vitro significantly better than naive whole-spleen cells. These results suggest that formulating BCG in DDA/TDB adjuvant confers superior protection in immunocompromised mice and likely involves the induction of long-lived memory DN T cells. PMID:27226281

  19. Mycobacterium tuberculosis virulence: insights and impact on vaccine development.

    Science.gov (United States)

    Delogu, Giovanni; Provvedi, Roberta; Sali, Michela; Manganelli, Riccardo

    2015-01-01

    The existing TB vaccine, the attenuated Mycobacterium bovis strain BCG, is effective in protecting infants from severe forms of the disease, while its efficacy in protecting adults from pulmonary TB is poor. In the last two decades, a renewed interest in TB resulted in the development of several candidate vaccines that are now entering clinical trials. However, most of these vaccines are based on a common rationale and aim to induce a strong T-cell response against Mycobacterium tuberculosis. Recent advancements in the understanding of M. tuberculosis virulence determinants and associated pathogenic strategies are opening a new and broader view of the complex interaction between this remarkable pathogen and the human host, providing insights at molecular level that could lead to a new rationale for the design of novel antitubercular vaccines. A vaccination strategy that simultaneously targets different steps in TB pathogenesis may result in improved protection and reduced TB transmission. PMID:26119086

  20. A NOVEL BCG SENSOR-ARRAY FOR UNOBTRUSIVE CARDIAC MONITORING

    Directory of Open Access Journals (Sweden)

    Anna Böhm

    2013-12-01

    Full Text Available Unobtrusive heart rate monitoring is a popular research topic in biomedical engineering. The reason is that convential methods, e.g. the clinical gold standard electrocardiography, require conductive contact to the human body. Other methods such as ballistocardiography try to record these vital signs without electrodes that are attached to the body. So far, these systems cannot replace routine procedures. Most systems have some drawbacks that cannot be compensated, such as aging of the sensor materials or movement artifacts. In addition, the signal form differs greatly from an ECG, which is an electrical signal. The ballistocardiogram has a mechanical source, which makes it harder to evaluate. We have developed a new sensor array made of near-IR-LEDs to record BCGs. IR-sensors do not age in relevant time scales. Analog filtering was neccesary, because the signal amplitude was very small. The digitized data was then processed by various algorithms to extract beat-to-beat or breath-to-breath intervals. The redundancy of multiple BCG channels was used to provide a robust estimation of beat-to-beat intervals and heart rate. We installed the system beneath a mattress topper of a hospital bed, but any other bed would have been sufficient. The validation of this measurement system shows that it is well suited for BCG recordings. The use of multiple channels has proven to be superior to relying on a single BCG channel.

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

    International Nuclear Information System (INIS)

    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 106 irradiated tumour cells each 1 to 3 weeks before administration of 1 x 106 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)

  2. BCG Artifact Removal for Reconstructing Full-scalp EEG inside the MR Scanner

    OpenAIRE

    Xia, Hongjing; Ruan, Dan; Cohen, Mark S.

    2013-01-01

    In simultaneous EEG/fMRI acquisition, the ballistocardiogram (BCG) artifact presents a major challenge for meaningful EEG signal interpretation and needs to be removed. This is very difficult, especially in continuous studies where BCG cannot be removed with averaging. In this study, we take advantage of a high-density EEG-cap and propose an integrated learning and inference approach to estimate the BCG contribution to the overall noisy recording. In particular, we present a special-designed ...

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

    International Nuclear Information System (INIS)

    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

  4. The management of BCG failure in non-muscle-invasive bladder cancer: an update

    OpenAIRE

    Zlotta, Alexandre R.; Fleshner, Neil E.; Jewett, Michael A.

    2009-01-01

    Up to 40% of patients with non-muscle-invasive bladder cancer (NMIBC) will fail intravesical bacillus Calmette-Guérin (BCG) therapy. There is unfortunately no current gold standard for salvage intravesical therapy after appropriate BCG treatment. Indeed, outcomes are at best suboptimal. The vast majority of low-grade NMIBC are prone to recur but very rarely progress. Failure after intravesical BCG in these patients is usually superficial and low-grade. At the other end of the spectrum, failur...

  5. Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

    Directory of Open Access Journals (Sweden)

    Eric Gomez

    2009-01-01

    Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

  6. Difference in antigen-presenting ability of macrophages between high- and low-responder mice in delayed-type hypersensitivity to Mycobacterium bovis BCG.

    OpenAIRE

    Nakamura, R. M.; Tokunaga, T; Yamamoto, S.

    1980-01-01

    Purified protein derivative-pulsed spleen macrophages of Mycobacterium bovis BCG high-responder mice stimulated BCG-primed lymphocytes of F1 (low x high) mice well in vitro, but those of BCG low-responder mice did not.

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

    International Nuclear Information System (INIS)

    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)

  8. Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice.

    OpenAIRE

    Huygen, K.; Abramowicz, D.; Vandenbussche, P; Jacobs, F.; De Bruyn, J; Kentos, A.; Drowart, A; van Vooren, J P; Goldman, M.

    1992-01-01

    Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular ...

  9. Pneumococcal vaccine.

    OpenAIRE

    1999-01-01

    Streptococcus pneumoniae is a frequent cause of pneumonia and meningitis. This article looks at the pneumococcal vaccine, its uses, efficacy, and adverse effects and how vaccination may be improved. We also look at the role of the new conjugate vaccines.

  10. Polio Vaccination

    Science.gov (United States)

    ... to its advantages over IPV in providing intestinal immunity and providing secondary spread of the vaccine to unprotected contacts. Who needs this vaccine and when? Side Effects Excerpt from Vaccine Information Statement A Polio-Free ...

  11. Smallpox Vaccination

    Science.gov (United States)

    ... Newsletters Events Also Known As Smallpox = Vaccinia Smallpox Vaccination Recommend on Facebook Tweet Share Compartir The smallpox ... like many other vaccines. For that reason, the vaccination site must be cared for carefully to prevent ...

  12. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. PMID:26541249

  13. [From genetics to genomics in the rational design of new Mycobacterium tuberculosis vaccines].

    Science.gov (United States)

    Bocanegra-García, Virgilio; Valencia-Delgadillo, Jorge; Cruz-Pulido, Wendy; Cantú-Ramírez, Rubén; Rivera-Sánchez, Gildardo; Palma-Nicolás, José Prisco

    2011-10-01

    Tuberculosis (TB) is an infectious disease affecting people from all ages all over the world. It is estimated that one third of the world population lives infected with the causal agent: Mycobacterium tuberculosis. Despite availability and systematic administration of BCG vaccine in endemic areas, TB transmission remains elusive to control, partly because BGC efficacy has been shown to have wide variability (0-80%). Such variability in protection is attributed to factors including: the BCG strain used for immunization, pre-existing exposure to environmental saprophytic Mycobacterium species, and host genetic factors. In this context, efforts regarding to re-engineering BCG vaccines with the ability to prevent latent TB reactivation, providing long lasting protection, and devoid from collateral effects in immunosuppressed people are urgent. In this work we review the actual molecular «gene-by-gene» strategies aimed at generating BCG alternatives, and discuss the urgent necessity of high throughput technology methods for a rational design for a new TB vaccine. PMID:21684635

  14. Assessment of phagosomes infected with Mycobacterium tuberculosis as a vaccine candidate against tuberculosis.

    Science.gov (United States)

    Sharma, Anjana; Parihar, Pankaj; Sharma, Juhi

    2014-11-01

    The present study describes a novel and simple vaccination strategy that involve culturing of M. tuberculosis in the macrophage cells. Isolation of phagosome from macrophage (cell line J774) infected with M. tuberculosis (H37) and M. bovis (BCG) at early and late phase of infection was done ensuing the identification and characterization of these phagosome. In vitro study of apoptosis induced by phagosome infected with (H37) and (BCG) was performed. The vaccine candidate with H1137 MOI- 1:10 at 3 h, MOI- 1:20 at 1, 1.5, 2.5 and 3 h and BCG MOI- 1:20 at 3.5 h showed percentage apoptosis as 38.64, 39.93, 34.66, 22.56,34.59 and 37.81% respectively. The results designates that macrophages provide cellular niche during infection and illustrate considerable immunogenic property. Novel antigens expressed or secreted by H37 in infected macrophages can provide evidence to be a successful vaccine candidate as it endures enhanced immune response than BCG. PMID:25434104

  15. Childhood vaccination in informal urban settlements in Nairobi, Kenya: Who gets vaccinated?

    Directory of Open Access Journals (Sweden)

    Ettarh Remare R

    2011-01-01

    Full Text Available Abstract Background Recent trends in global vaccination coverage have shown increases with most countries reaching 90% DTP3 coverage in 2008, although pockets of undervaccination continue to persist in parts of sub-Saharan Africa particularly in the urban slums. The objectives of this study were to determine the vaccination status of children aged between 12-23 months living in two slums of Nairobi and to identify the risk factors associated with incomplete vaccination. Methods The study was carried out as part of a longitudinal Maternal and Child Health study undertaken in Korogocho and Viwandani slums of Nairobi. These slums host the Nairobi Urban Health and Demographic Surveillance System (NUHDSS run by the African Population and Health Research Centre (APHRC. All women from the NUHDSS area who gave birth since September 2006 were enrolled in the project and administered a questionnaire which asked about the vaccination history of their children. For the purpose of this study, we used data from 1848 children aged 12-23 months who were expected to have received all the WHO-recommended vaccinations. The vaccination details were collected during the first visit about four months after birth with follow-up visits repeated thereafter at four month intervals. Full vaccination was defined as receiving all the basic childhood vaccinations by the end of 24 months of life, whereas up-to-date (UTD vaccination referred to receipt of BCG, OPV 1-3, DTP 1-3, and measles vaccinations within the first 12 months of life. All vaccination data were obtained from vaccination cards which were sighted during the household visit as well as by recall from mothers. Multivariate models were used to identify the risk factors associated with incomplete vaccination. Results Measles coverage was substantially lower than that for the other vaccines when determined using only vaccination cards or in addition to maternal recall. Up-to-date (UTD coverage with all vaccinations

  16. Testing a molasses-based bait for oral vaccination of white-tailed deer (Odocoileus virginianus) against Mycobacterium bovis

    Science.gov (United States)

    White-tailed deer (Odocoileus virginianus) in Michigan, USA are wildlife reservoirs of bovine tuberculosis (bTB) with documented spread to cattle. In vaccine efficacy trials, Mycobacterium bovis bacillus Calmette Guerin (BCG) administered orally reduces colonization and bTB-associated lesions in whi...

  17. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice.

    Science.gov (United States)

    Aguilo, Nacho; Uranga, Santiago; Marinova, Dessislava; Monzon, Marta; Badiola, Juan; Martin, Carlos

    2016-01-01

    Development of novel more efficient preventive vaccines against tuberculosis (TB) is crucial to achieve TB eradication by 2050, one of the Millennium Development Goals (MDG) for the current century. MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis developed as BCG-replacement strategy in newborns that has entered first-in-human adult clinical trials. In this work, we characterize the safety, immunogenicity and protective efficacy of MTBVAC in a model of newborn C57/BL6 mice. Our data clearly indicate that MTBVAC is safe for newborn mice, and does not affect animal growth or organ development. In addition, MTBVAC-vaccinated mice at birth showed enhanced immunogenicity and better protection against M. tuberculosis challenge in comparison with BCG. PMID:26786657

  18. BCG-Induced Dendritic Cell Responses and Suppression of Interleukin-5 Production from T Cells in Atopic Asthmatics

    OpenAIRE

    Choi, Inseon S.; Lin, Xiang-Hua; Koh, Young-Ah; Cui, Yong

    2008-01-01

    Bacille Calmette-Guérin (BCG) induces potent Th1 responses with the help of interleukin (IL)-10 and IL-12 released from dendritic cells (DCs), and suppresses Th2-associated allergic reactions. However, there are still some controversies on therapeutic effects of BCG in asthmatics. This study investigated whether BCG administration to DCs suppresses IL-5 production from T cells in atopic asthmatics. DCs derived from peripheral blood of subjects were cultured with or without BCG and Dermatophag...

  19. Adolescent Vaccination

    OpenAIRE

    Mustafa Hacımustafaoğlu

    2008-01-01

    Adolescent period usually are omitted regarding the vaccination and the other health evaluations, in our country. Adolescent period is usually considered as between the ages of 8-18 years. During this period, it is important to evaluate routine adolescent examination as well as vaccination status.Childhood (0-18 years) vaccination can be considered in three stages; infantil period vaccinations (

  20. Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice.

    Science.gov (United States)

    Li, Wu; Li, Min; Deng, Guangcun; Zhao, Liping; Liu, Xiaoming; Wang, Yujiong

    2015-08-01

    Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection. PMID:25962477

  1. Using a prime and pull approach, lentivector vaccines expressing Ag85A induce immunogenicity but fail to induce protection against Mycobacterium bovis bacillus Calmette-Guérin challenge in mice.

    Science.gov (United States)

    Britton, Gary; MacDonald, Douglas C; Brown, Jeremy S; Collins, Mary K; Goodman, Anna L

    2015-10-01

    Although bacillus Calmette-Guérin (BCG) is an established vaccine with excellent efficacy against disseminated Mycobacterium tuberculosis infection in young children, efficacy in adults suffering from respiratory tuberculosis (TB) is suboptimal. Prime-boost viral vectored vaccines have been shown to induce effective immune responses and lentivectors (LV) have been shown to improve mucosal immunity in the lung. A mucosal boost to induce local immunogenicity is also referred to as a 'pull' in a prime and pull approach, which has been found to be a promising vaccine strategy. The majority of infants worldwide receive BCG immunization through current vaccine protocols. We therefore aimed to investigate the role of a boost (or pull) immunization with an LV vaccine expressing the promising TB antigen (Ag85A). We immunized BALB/c mice subcutaneously with BCG or an LV vaccine expressing a nuclear factor-κB activator vFLIP together with Ag85A (LV vF/85A), then boosted with intranasal LV vF/85A. Prime and pull immunization with LV85A induced significantly enhanced CD8(+) and CD4(+) T-cell responses in the lung, but did not protect against intranasal BCG challenge. In contrast, little T-cell response in the lung was seen when the prime vaccine was BCG, and intranasal vF/85A provided no additional protection against mucosal BCG infection. Our study demonstrates that not all LV prime and pull approaches may be successful against TB in man and careful antigen and immune activator selection is therefore required. PMID:26095282

  2. 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.

  3. Bacillus Calmette-Guérin vaccination at birth

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    OUTCOME MEASURES: The Danish Calmette Study is a randomized, clinical trial. The study was conducted at three university hospitals and randomized 4262 children of gestational age ≥32weeks to receive BCG within seven days of birth or to a no-intervention control group. Follow-up consisted of clinical......BACKGROUND: Bacillus Calmette-Guérin vaccine (BCG) induces a complex, pro-inflammatory immune response. Obesity is associated with low-grade inflammation. AIMS: The purpose of the study was to test whether BCG at birth has effects on infant growth and body composition. STUDY DESIGN, SUBJECTS, AND......-up was 94% complete at 3 and 13months after birth. The children were bigger than the WHO reference population. There was no effect of BCG on weight z-score at 13months (-0.028 [95% confidence interval: -0.085 to 0.029], p=0.34). There was no effect on weight and length at 3months, or length, mid...

  4. Systemic BCG infection in a patient with pancytopaenia and fever 9 years after intravesical BCG administration for bladder cancer.

    Science.gov (United States)

    Westhovens, Ine M; Vanden Abeele, Marie-Elena; Messiaen, Peter E; van der Hilst, Jeroen Ch

    2016-01-01

    BCG is an attenuated live strain of Mycobacterium bovis that is used as an intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG instillation can lead to systemic diseases. We present a case of a 75-year-old man who was treated for recurrent localised transitional cell carcinoma (TCC) of the bladder with intravesical instillation of BCG in 2006. His medical history included Parkinson's disease. The patient reported worsening of Parkinson symptoms in the preceding month. In addition, he had progressive pancytopaenia and a bone marrow biopsy showed a granulomatous inflammatory infiltrate. Cultures from bone marrow aspiration grew M. bovis He was successfully treated with tuberculostatic drugs and made a full recovery. In addition, there was partial amelioration of the Parkinson symptoms. This case shows that physicians should be aware that BCG instillation for TCC can cause systemic disease even years after treatment. PMID:27170615

  5. Aromatic-dependent salmonella as anti-bacterial vaccines and as presenters of heterologous antigens or of DNA encoding them.

    Science.gov (United States)

    Stocker, B A

    2000-09-29

    The development of live bacterial vaccines is reviewed, in particular aromatic-dependent Salmonella, either for protection against the corresponding infections (including typhoid fever) or as carrier-presenter of antigens of unrelated pathogens or of DNA specifying them. Aromatic-dependent Salmonella live vaccines are also compared with BCG and Ty21a and the recent records of exceptional situations are discussed in which aroA (deletion) strains of Salmonella typhimurium cause progressive disease in mice. PMID:11000459

  6. Code system BCG for gamma-ray skyshine calculation

    International Nuclear Information System (INIS)

    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)

  7. Skirtingu laiku BCG vakcinomis skiepytų vaikų tuberkulino reakcijos ikimokykliniu laikotarpiu

    OpenAIRE

    Sučilienė, Elena

    2010-01-01

    Disertacijos objektas: įvairių BCG skiepijimo režimų įtaka tuberkulino reakcijos išraiškai, vietinei BCG žymei, specifinei serologijai, alergijos klinikai vaikams iki 6 m. Tyrime dalyvavo 509 vaikai, vakcinuoti įprasta arba pusine BCG vakcinos doze naujagimio ar 3 mėn. amžiaus. Jiems 3 mėn. po BCG vakcinacijos, 1, 2 ir 6 m. atliktas tuberkulino mėginys, įvertintas BCG randelis, ištirti specifiniai antikūnai kraujo serume, įvertintos alerginės būklės. Disertacijos išvadose konstatuojama, kad 3...

  8. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  9. 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.

  10. Validity of self-reported vaccination status among French healthcare students.

    Science.gov (United States)

    Loulergue, P; Pulcini, C; Massin, S; Bernhard, M; Fonteneau, L; Levy-Brühl, D; Guthmann, J-P; Launay, O

    2014-12-01

    Data on validity of self-reported vaccinations are scarce. This study, performed on healthcare students in Paris (France), aimed to evaluate this validity for occupational vaccinations. The validity of self-reported vaccination status was compared with written information. A total of 432 students were enrolled. Sensitivity rates for BCG, hepatitis B and measles were over 74%. For diphtheria-tetanus-polio and pertussis, sensitivity was below 50%. Specificity was between 70 and 95% for dTP-pertussis, and below 35% for all others. Overall, the validity of self-reported information was low, meaning that checking medical records remains the preferable strategy for assessing immunization status. PMID:25040583

  11. Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

    Science.gov (United States)

    Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

    2016-06-01

    Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

  12. Antibody response to 17D yellow fever vaccine in Ghanaian infants.

    OpenAIRE

    2001-01-01

    OBJECTIVES: To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. METHODS: Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous inj...

  13. Towards new TB vaccines: What are the challenges?

    Science.gov (United States)

    Dockrell, Hazel M

    2016-06-01

    New and effective tuberculosis (TB) vaccines are urgently needed to control pulmonary TB, and in particular to prevent the spread of drug-resistant strains of Mycobacterium tuberculosis. These drug-resistant strains can range from those resistant to first-line drugs to those that are almost impossible to treat. To develop new and effective vaccines for HIV and malaria has been difficult and it is proving to be just as challenging for TB. TB is a complicated disease with a spectrum from apparently controlled latent infection to active clinical disease and so different types of preventive or post-exposure vaccine may be needed. Identifying the most promising vaccine candidates to move into clinical trials is difficult, as we lack biomarker signatures that can predict protective efficacy. There is a risk that the failure of the MVA-85A vaccine to show efficacy when given to previously BCG-vaccinated South African infants will impact on the resources available for the development and trials of other candidate TB vaccines. Continued support for the development of new TB vaccines should remain a priority as an effective vaccine would bring huge public health benefits. PMID:26960944

  14. Restoration of proliferative response to M. leprae antigens in lepromatous T cells against candidate antileprosy vaccines.

    Science.gov (United States)

    Mustafa, A S

    1996-09-01

    Several studies conducted in the last decade suggest that Mycobacterium lepraereactive T cells exist in lepromatous patients, but their number may be too few to yield a detectable response in cell-mediated immunity (CMI) assays. Immunizations with candidate antileprosy vaccines and stimulation of T cells with M. leprae + interleukin-2 restore the M. leprae-induced CMI response in lepromatous leprosy patients. These immunizations and stimulation may enrich the pre-existing M. leprae-responsive T cells in lepromatous patients and, thereby, induce a detectable CMI response to M. leprae antigens upon repeat testing. To verify this proposition, we carried out a study in a group of 10 lepromatous leprosy patients. Peripheral blood mononuclear cells (PBMC) obtained from these patients were anergic to M. leprae antigens in proliferative assays, but they responded to the antigens of candidate antileprosy vaccines, i.e., M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. The enrichment of M. leprae-responsive T cells was performed by establishing T-cell lines from the PBMC after in vitro stimulation with M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. When tested for their proliferative responses, 1/10, 3/10, 6/10 and 2/10 T-cell lines established against M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w, respectively, responded to M. leprae. These results suggest that enrichment of pre-existing M. leprae-responsive T cells may contribute to the restoration of the T-cell response to M. leprae in some lepromatous patients. Four of the 10 M. leprae-induced T-cell lines proliferated in response to the 65 kDa, 36 kDa, 28 kDa, and 12 kDa recombinant antigens of M. leprae, suggesting that the nonresponsiveness of T cells in some lepromatous patients may be overcome by using recombinant antigens of M. leprae. PMID:8862259

  15. Twin SMBH candidates in the BCG of RBS 797

    CERN Document Server

    Gitti, Myriam; Giovannini, Gabriele; Feretti, Luigina; Liuzzo, Elisabetta

    2015-01-01

    The radio-loud BCG at the center of the cool core cluster RBS 797 is known to exhibit a misalignment of its 5 GHz radio emission observed at different VLA resolutions, with the innermost kpc-scale jets being almost orthogonal to the radio lobes which extends for tens of kpc filling the X-ray cavities seen by Chandra. The different radio directions may be caused by rapid jet reorientation due to interaction with a secondary supermassive black hole (SMBH), or to the presence of two AGN, probably in a merging phase, which are emitting radio jets in different directions. We present the results of new 5 GHz observations performed with the EVN in May 2013. In particular, we detected two compact radio components, with a projected separation of 77 pc. We discuss two possible scenarios for the origin and nature of the EVN double source, showing that both interpretations are consistent with the presence of a SMBH binary system in the BCG of RBS 797.

  16. Cosmological Constraints From SDSS MaxBCG Cluster Abundances

    International Nuclear Information System (INIS)

    We perform a maximum likelihood analysis of the cluster abundance measured in the SDSS using the maxBCG cluster finding algorithm. Our analysis is aimed at constraining the power spectrum normalization σ8, and assumes flat cosmologies with a scale invariant spectrum, massless neutrinos, and CMB and supernova priors (Omega)mh2 = 0.128 ± 0.01 and h = 0.72 ± 0.05 respectively. Following the method described in the companion paper Rozo et al. (2007), we derive σ8 = 0.92 ± 0.10 (1σ) after marginalizing over all major systematic uncertainties. We place strong lower limits on the normalization, σ8 > 0.76 (95% CL) (> 0.68 at 99% CL). We also find that our analysis favors relatively low values for the slope of the Halo Occupation Distribution (HOD), α = 0.83 ± 0.06. The uncertainties of these determinations will substantially improve upon completion of an ongoing campaign to estimate dynamical, weak lensing, and X-ray cluster masses in the SDSS maxBCG cluster sample

  17. Evaluation of two different dendritic cell preparations with BCG reactivity

    Directory of Open Access Journals (Sweden)

    Fol Marek

    2016-01-01

    Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

  18. Estimation of nationwide vaccination coverage and comparison of interview and telephone survey methodology for estimating vaccination status.

    Science.gov (United States)

    Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong; Park, Sue K

    2011-06-01

    This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

  19. Determinants of vaccination coverage in rural Nigeria

    Directory of Open Access Journals (Sweden)

    Meurice Francois P

    2008-11-01

    Full Text Available Abstract Background Childhood immunization is a cost effective public health strategy. Expanded Programme on Immunisation (EPI services have been provided in a rural Nigerian community (Sabongidda-Ora, Edo State at no cost to the community since 1998 through a privately financed vaccination project (private public partnership. The objective of this survey was to assess vaccination coverage and its determinants in this rural community in Nigeria Methods A cross-sectional survey was conducted in September 2006, which included the use of interviewer-administered questionnaire to assess knowledge of mothers of children aged 12–23 months and vaccination coverage. Survey participants were selected following the World Health Organization's (WHO immunization coverage cluster survey design. Vaccination coverage was assessed by vaccination card and maternal history. A child was said to be fully immunized if he or she had received all of the following vaccines: a dose of Bacille Calmette Guerin (BCG, three doses of oral polio (OPV, three doses of diphtheria, pertussis and tetanus (DPT, three doses of hepatitis B (HB and one dose of measles by the time he or she was enrolled in the survey, i.e. between the ages of 12–23 months. Knowledge of the mothers was graded as satisfactory if mothers had at least a score of 3 out of a maximum of 5 points. Logistic regression was performed to identify determinants of full immunization status. Results Three hundred and thirty-nine mothers and 339 children (each mother had one eligible child were included in the survey. Most of the mothers (99.1% had very positive attitudes to immunization and > 55% were generally knowledgeable about symptoms of vaccine preventable diseases except for difficulty in breathing (as symptom of diphtheria. Two hundred and ninety-five mothers (87.0% had a satisfactory level of knowledge. Vaccination coverage against all the seven childhood vaccine preventable diseases was 61.9% although it

  20. Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study

    Directory of Open Access Journals (Sweden)

    Menzies Dick

    2011-01-01

    Full Text Available Abstract Background The development of a successful new tuberculosis (TB vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course (DOTS and current level of bacille Calmette-Guérin (BCG vaccination coverage. Methods We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005 in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398% of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. Results Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated. This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated. With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial

  1. On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines.

    Science.gov (United States)

    Arregui, Sergio; Sanz, Joaquín; Marinova, Dessislava; Martín, Carlos; Moreno, Yamir

    2016-01-01

    Over the past 60 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used worldwide to prevent tuberculosis (TB). However, BCG has shown a very variable efficacy in different trials, offering a wide range of protection in adults against pulmonary TB. One of the most accepted hypotheses to explain these inconsistencies points to the existence of a pre-existing immune response to antigens that are common to environmental sources of mycobacterial antigens and Mycobacterium tuberculosis. Specifically, two different mechanisms have been hypothesized to explain this phenomenon: the masking and the blocking effects. According to masking hypothesis, previous sensitization confers some level of protection against TB that masks vaccine's effects. In turn, the blocking hypothesis postulates that previous immune response prevents vaccine taking of a new TB vaccine. In this work we introduce a series of models to discriminate between masking and blocking mechanisms and address their relative likelihood. We apply our methodology to the data reported by BCG-REVAC clinical trials, which were specifically designed for studying BCG efficacy variability. Our results yield estimates that are consistent with high levels of blocking (41% in Manaus -95% CI [14-68]- and 96% in Salvador -95% CI [52-100]-). Moreover, we also show that masking does not play any relevant role in modifying vaccine's efficacy either alone or in addition to blocking. The quantification of these effects around a plausible model constitutes a relevant step towards impact evaluation of novel anti-tuberculosis vaccines, which are susceptible of being affected by similar effects, especially if applied on individuals previously exposed to mycobacterial antigens. PMID:26893956

  2. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... HPV is a common virus that is spread through sexual contact. There are several types of HPV. ...

  3. Diphtheria Vaccination

    Science.gov (United States)

    ... children and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination Pronounced (dif-THEER-ee-a) Recommend on Facebook Tweet Share Compartir Diphtheria causes a thick covering in the back of ...

  4. A combined DNA vaccine provides protective immunity against Mycobacterium bovis and Brucella abortus in cattle.

    Science.gov (United States)

    Hu, Xi-Dan; Yu, Da-Hai; Chen, Su-Ting; Li, Shu-Xia; Cai, Hong

    2009-04-01

    We evaluated the immunogenicity and protective efficacy of a combined DNA vaccine containing six genes encoding immunodominant antigens from Mycobacterium bovis and Brucella abortus. The number of lymph node and spleen cultures positive for M. bovis and B. abortus from calves immunized with the combined DNA vaccine was significantly reduced (p abortus 544. The combined DNA vaccine group displayed stronger antigen-specific interferon-gamma (IFN-gamma) responses and antigen-specific IFN-gamma ELISPOT activities 2 months after final immunization and after challenge. Antigen-specific CD4(+) and CD8(+) T cell responses in the combined DNA vaccine group were higher than either the Bacillus Calmette-Guerin (BCG)-positive or S19-positive control group. Likewise, more calves in the DNA vaccine group exhibited antigen-specific IgG titers and had higher IgG titers than those in the BCG- or S19-immunized groups 2 months after the final immunization. Moreover, two antigens in the combined DNA vaccine induced significant antigen-specific IFN-gamma responses 6 months after challenge (p S19 against B. abortus. This is the first report to demonstrate that a single combined DNA vaccine protects cattle against two infectious diseases. PMID:19364278

  5. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes.

    OpenAIRE

    O'Donnell, M A; Aldovini, A; Duda, R B; Yang, H; Szilvasi, A; Young, R A; DeWolf, W C

    1994-01-01

    Mycobacterium bovis BCG was genetically engineered to express and secrete mouse interleukin-2 (IL-2) and rat IL-2. Genes encoding IL-2 were inserted into an Escherichia coli-BCG shuttle plasmid under the control of the BCG HSP60 promoter. To facilitate study of proteins produced in this system, the IL-2 gene product was expressed (i) alone, (ii) with the mycobacterial alpha-antigen secretion signal sequence at the amino terminus, (iii) with an influenza virus hemagglutinin epitope tag at the ...

  6. A COMBINED FULL-WAVE BCG-FFT METHOD FOR RADIATION OF MICROSTRIP ANTENNA ARRAYS

    Institute of Scientific and Technical Information of China (English)

    Zhang Hou; Peng Hongli; Liu Qizhong; Yin Yingzeng; Gong Shuxi

    2001-01-01

    A method of combining BiConjugate Gradient(BCG) with Fast Fourier Transform(FFT) to analyze the radiation of microstrip antenna arrays is presented, where the spatially discrete BCG-FFT for analyzing microstrip structure is used and the del operators on Green's functions are transferred from the singular kernel to the expansion and testing functions. The resultant equations are solved by using BCG method in which the matrix-vector product is evaluated efficiently with FFT. The calculated patterns are in good agreement with the measured data.

  7. "A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City "

    Directory of Open Access Journals (Sweden)

    Akefeh Ahmadiafshar

    2005-12-01

    Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013, atopic dermatitis (P<0.01, and atopy (P<0.01. We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.

  8. Pneumococcal Vaccines

    OpenAIRE

    Chen-Fang Ho; Tzou-Yien Lin

    2005-01-01

    Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases inchildren and adolescents. The 23-valent pneumococcal polysaccharide vaccine could preventinvasive pneumococcal infection with broader serotype coverage but still has some limitations.On the other hand, 7-valent pneumococcal conjugate vaccine has been shown todecrease cases of nasopharyngeal acquired S. pneumoniae vaccine serotypes and provedherd immunity. The safety and efficacy against vaccine serotype pneumo...

  9. DNA vaccines

    OpenAIRE

    Coban, Cevayir; Kobiyama, Kouji; Jounai, Nao; Tozuka, Miyuki; Ishii, Ken J.

    2013-01-01

    Since the introduction of DNA vaccines two decades ago, this attractive strategy has been hampered by its low immunogenicity in humans. Studies conducted to improve the immunogenicity of DNA vaccines have shown that understanding the mechanism of action of DNA vaccines might be the key to successfully improving their immunogenicity. Our current understanding is that DNA vaccines induce innate and adaptive immune responses in two ways: (1) encoded protein (or polypeptide) antigen(s) by the DNA...

  10. Recent advances in the development of vaccines for tuberculosis.

    Science.gov (United States)

    Ahsan, Mohamed Jawed

    2015-05-01

    Tuberculosis (Tb) continues to be a dreadful infection worldwide with nearly 1.5 million deaths in 2013. Furthermore multi/extensively drug-resistant Tb (MDR/XDR-Tb) worsens the condition. Recently approved anti-Tb drugs (bedaquiline and delamanid) have the potential to induce arrhythmia and are recommended in patients with MDR-Tb when other alternatives fail. The goal of elimination of Tb by 2050 will not be achieved without an effective new vaccine. The recent advancement in the development of Tb vaccines is the keen focus of this review. To date, Bacille Calmette Guerin (BCG) is the only licensed Tb vaccine in use, however its efficacy in pulmonary Tb is variable in adolescents and adults. There are nearly 15 vaccine candidates in various phases of clinical trials, includes five protein or adjuvant vaccines, four viral-vectored vaccines, three mycobacterial whole cell or extract vaccines, and one each of the recombinant live and the attenuated Mycobacterium tuberculosis (Mtb) vaccine. PMID:26288734

  11. Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

    Science.gov (United States)

    Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

    2000-04-01

    Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity. PMID:10728599

  12. Recombinant Yellow Fever Vaccine Virus 17D Expressing Simian Immunodeficiency Virus SIVmac239 Gag Induces SIV-Specific CD8+ T-Cell Responses in Rhesus Macaques ▿

    OpenAIRE

    Bonaldo, Myrna C.; Martins, Mauricio A.; Rudersdorf, Richard; Mudd, Philip A.; Sacha, Jonah B.; Piaskowski, Shari M.; Costa Neves, Patrícia C.; Veloso de Santana, Marlon G.; Vojnov, Lara; Capuano, Saverio; Rakasz, Eva G.; Wilson, Nancy A.; Fulkerson, John; Sadoff, Jerald C.; Watkins, David I.

    2010-01-01

    Here we describe a novel vaccine vector for expressing human immunodeficiency virus (HIV) antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8+ T-cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8+ T-cell responses after recombinant YF17D boosting. These recombinan...

  13. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  14. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG

    Science.gov (United States)

    ten Have, R.; Reubsaet, K.; van Herpen, P.; Kersten, G.; Amorij, J.-P.

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG. PMID:26981867

  15. Developing vaccines to prevent sustained infection with Mycobacterium tuberculosis: Conference proceedings: National Institute of Allergy and Infectious Diseases, Rockville, Maryland USA, November 7, 2014.

    Science.gov (United States)

    2015-06-12

    On November 7, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a conference entitled "Vaccine Prevention of Sustained Mycobacterium tuberculosis Infection." The purpose of this meeting was to explore the biologic plausibility, potential public health and economic impact, and regulatory feasibility in attempting to develop a vaccine to prevent sustained infection with Mycobacterium tuberculosis (Mtb). Currently there are two main goals for tuberculosis (TB) vaccine development, to develop a vaccine that could serve as a booster to Bacille Calmette-Guérin (BCG) vaccination and prevent active TB in adolescents and adults, and to develop an improved vaccine to replace BCG in infants. Although prevention of sustained Mtb infection is being used as a proof of biological activity for vaccines in mid-Phase 2 development, there currently are no plans for pursuing a prevention of Mtb infection licensure indication for TB vaccines. Ultimately, pursuing a prevention of sustained Mtb infection indication for TB vaccines, in parallel with ongoing efforts to develop vaccines to prevent active TB disease, was deemed a potentially important effort, but would require further resources, particularly to improve diagnostic assays, to increase the regulatory feasibility of this endeavor. PMID:25869889

  16. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Pramod K Giri

    Full Text Available Activation of both CD4(+ and CD8(+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4(+ and CD8(+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4(+ and CD8(+ T cells. The isolated T cells also produced IFN-gamma upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate.

  17. Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

    Science.gov (United States)

    Rook, Graham A W; Dheda, Keertan; Zumla, Alimuddin

    2005-03-18

    Tuberculosis vaccine candidates are entering clinical studies in areas where BCG fails. This is a high-risk strategy. We suggest that geographical variation in the efficacy of BCG is related to the presence in developing countries of a cross-reactive background Th2-like response, probably attributable to exposure of mother and infant to helminths and environmental mycobacteria. Such Th2-like activity can stop Mycobacterium tuberculosis from being pushed into a latent state by the Th1 response, impair bactericidal functions and cause toxicity of TNF-alpha and pulmonary fibrosis. A successful vaccine, rather than driving a Th1 response, might need to suppress this pre-existing subversive Th2-like component. PMID:15755581

  18. [Sepsis and multiple organ failure after BCG instillation in bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-12-01

    Local Bacillus Calmette-Guerin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcino-ma. Local side effects are frequent, where-as systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer.A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma.4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal li-ver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed non-caseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15645554

  19. [Sepsis and multiple organ failure after BCG-instillation for bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-08-01

    Local Bacillus Calmette-Guérin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcinoma. Local side effects are frequent, whereas systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer. A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma. 4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal liver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed noncaseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15138643

  20. BCG vaccination status may predict sputum conversion in patients with pulmonary tuberculosis

    DEFF Research Database (Denmark)

    Jeremiah, Kidola; PrayGod, George; Faurholt-Jepsen, Daniel;

    2010-01-01

    Failure to convert (persistent sputum and/or culture positivity) while on antituberculosis (anti-TB) treatment at the end of the second month of anti-TB therapy has been reported to be a predictor of treatment failure. Factors that could be associated with persistent bacillary positivity at the e...