PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “BCG”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2005

Differential effects of prior exposure to environmental mycobacteria on vaccination with Mycobacterium bovis BCG or a recombinant BCG strain expressing RD1 antigens.

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 experimental tuberculosis (TB). No evidence that the RD1-encoded antigens ESAT-6, CFP-10, and PPE68 were expressed by these environmental strains could be demonstrated by Western blot analysis. Mice sensitized with each of these strains did not prime cellular immune responses cross-reacting with the immunodominant ESAT-6. Importantly, clearance of BCG::RD1 from the lungs and spleens of mice exposed to each of the environmental strains before vaccination was minimal compared to that of BCG. In mice sensitized with M. avium, increased persistence of BCG::RD1 correlated with stronger antimycobacterial gamma interferon responses and enhanced protection against aerosol infection with M. tuberculosis, compared to BCG. In contrast, animals exposed to M. scrofulaceum or M. vaccae prior to vaccination with BCG or BCG::RD1 were better protected against TB than were the unsensitized controls. Our results suggest that the inhibitory effect of environmental mycobacteria on the protective efficacy of BCG depends critically on the extent of cross-recognition of antigens shared with the vaccine. In hosts sensitized with M. avium, potent immunogenicity of ESAT-6 and increased persistence of BCG::RD1 may allow this recombinant vaccine to overcome preexisting antimycobacterial responses.

Animals↗
PubMed1995

Involvement of natural killer cells in nitric oxide production by spleen cells after stimulation with Mycobacterium bovis BCG. Study of the mechanism of the different abilities of viable and killed BCG.

Viable and killed BCG were compared for the ability to induce nitric oxide (NO) production in normal spleen cells and peritoneal exudate macrophages. Stimulation of spleen cells with viable BCG resulted in a strong expression of inducible NO synthase followed by an enhanced production of nitrite. However, those responses were not induced after stimulation with killed BCG or when macrophages were stimulated with killed and viable BCG. The same level of TNF-alpha mRNA expression was observed in reverse transcription-PCR after stimulation of spleen cells with viable and killed BCG. However, IFN-gamma production was induced only when spleen cells were stimulated with viable BCG. Concurrent stimulation of rIFN-gamma with either viable or killed BCG resulted in a strong nitrite production by macrophages. Neutralization of IFN-gamma and TNF-alpha caused a complete inhibition of nitrite production. Furthermore, anti-asialo GM1 Ab plus complement treatment abolished IFN-gamma production after stimulation with viable BCG, indicating that the NK cell was the major source of IFN-gamma, and its production was triggered only by stimulation with viable BCG. The present study showed that the ability of viable BCG to induce NO production is superior to that of killed BCG, and both IFN-gamma and TNF-alpha are essential for BCG-induced NO production by spleen cells. NK cells appeared to be important as a source of IFN-gamma, and the insufficient NO induction by killed BCG was due to the inability to induce IFN-gamma from NK cells.

Animals↗
PubMed1986

Control of the Bcg gene of early resistance in mice to infections with BCG substrains and atypical mycobacteria.

The effect of the Bcg gene on the early host response to intravenous infection with a variety of BCG substrains and some atypical mycobacteria was investigated. The numbers of live bacilli of BCG Pasteur and BCG Tice recovered from the spleens of Bcgs mice (C57BL/6, B10.A and BALB/c) at 3 weeks following infection exceeded the bacterial dose injected, whereas the number of CFU recovered from the spleens of Bcgr mice (A/J, DBA/2 and C3H/HeN) did not exceed the number of CFU injected, thus following the pattern observed in Bcgr mice and Bcgs infected with BCG Montreal. BCG Russia failed to multiply in both test groups; however, the number of CFU recovered in Bcgr mice was significantly lower than in Bcgs mice. On the other hand, the presence of live bacilli in the spleens of either Bcgr or Bcgs mice injected with BCG Japan was undetectable in most cases. Involvement of the Bcg gene in the early resistance to infection with BCG Pasteur, BCG Russia, Mycobacterium kansasii and M. intracellulare was documented by the significant differences in the kinetics of infections in mice of the C.D2 (BALB/c-Bcgr) and BALB/c (Bcgs) congenic lines. In BCG Russia, M. intracellulare and M. fortuitum infections, the phenotypic expression of the Bcg gene resulted in a more rapid elimination of the bacteria in the spleens of Bcgr when compared with Bcgs mice. On the other hand, the hepatic granuloma formation correlated with bacterial load except when C.D2 mice were infected with a small dose of BCG Pasteur or M. kansasii where extensive granulomatous hepatitis developed although no bacterial multiplication occurred in the spleen. It is suggested that granuloma formation could depend of the properties of the mycobacteria as well as the genetic background of the host without implicating the bacterial burden.

Animals↗
PubMed2005

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.

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 of calves (10 animals per group) was vaccinated subcutaneously with CFP formulated with Emulsigen and combined with a CpG oligodeoxynucleotide (ODN). A second group was vaccinated with both the CFP vaccine and BCG injected at adjacent sites (CFP-BCG). One further group was vaccinated subcutaneously with BCG, while another group served as nonvaccinated control animals. Vaccination with CFP-BCG induced levels of antigen-specific gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in whole-blood cultures that were higher than those induced by vaccination with BCG alone. The combination of CFP and BCG did not enhance the production of antibodies to M. bovis CFP compared to vaccination with CFP alone. Vaccination with CFP alone led to delayed antigen-specific IFN-gamma and IL-2 responses. Vaccination with CFP-BCG induced a high level of protection against an intratracheal challenge with virulent M. bovis, based on a significant enhancement of six pathological and microbiological parameters of protection compared with the nonvaccinated group. In contrast, vaccination with BCG alone induced a significant enhancement of protection in only one parameter, while CFP alone induced no protection. These results suggest that a combination of a CpG ODN-formulated protein vaccine and BCG offers better protection against bovine tuberculosis than does BCG alone.

Adjuvants, Immunologic↗
PubMed2003

BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.

Adjuvants, Immunologic↗
PubMed2000

Bacille Calmette-Guérin (BCG)-associated inflammation and fibrosis: modulation by recombinant BCG expressing interferon-gamma (IFN-gamma).

Immunization with existing BCG vaccines has failed to confer consistent protection against tuberculosis. One of the ways to improve the efficacy of BCG is by enhancing its ability to induce a type-1 T cell response. However, this approach carries the risk that enhanced immunoreactivity may exacerbate tissue pathology associated with vaccination. The aim of the present study was to determine whether use of a recombinant BCG expressing IFN-gamma (BCG-IFN) would result in an alteration in the pattern of inflammation and local tissue fibrosis. A murine intravenous BCG infection model was used in which there was a time- and dose-dependent increase in the weight and number of granulomas in the liver. Infection was associated with increased inflammatory activity in the liver, as shown by the increase in expression of inducible nitric oxide synthase (iNOS) assessed by immunochemistry and by measurement of specific mRNA, and in fibrosis measured by hydroxyproline content of the liver and percentage of granuloma cells staining positively for type 1 procollagen. Infection with BCG-IFN resulted in a reduction in organ weight and bacterial load on day 21 compared with infection with control BCG transformed with vector alone (BCG-plasmid). By day 21, there was also a reduction in iNOS mRNA and iNOS+ cells in granulomas in mice infected with BCG-IFN compared with infection with BCG-plasmid, and a similar reduction in both total number of granulomas and liver hydroxyproline content. These results demonstrate that the granulomas in the areas of mycobacterial infection are active sites of both inflammation and fibrosis, and that the local expression of IFN-gamma by the recombinant BCG results in more efficient bacterial clearance which is accompanied by a reduction in tissue pathology.

Animals↗
PubMed1985

BCG test reaction in previously BCG vaccinated children.

BCG test reactions were studied in 1095 non-tuberculous children from 6 months to 5 years of age, who had received BCG vaccination in the newborn period, in order to find out the diagnostic value of the BCG test in previously BCG vaccinated children. Previous BCG vaccination has an effect on the BCG test reaction in the form of an accelerated BCG reaction. Although the degree of reaction decreases with time, 51.4% of children still showed a strongly accelerated BCG reaction 4 1/2-5 years after BCG vaccination. It is concluded that the BCG test cannot be used as a diagnostic test for tuberculosis in children under 5 years of age who have had previous BCG vaccination.

Age Factors↗
PubMed1976

Effects of BCG (Bacillus Calmette-Guérin) vaccines on immune responses in mice. I. Possible effect of BCG on helper T cells.

The effects of killed and living BCG on antibody production against hamster erythrocytes (HRBC) and the 2, 4, 6-trinitrophenyl (TNP) group were studied in SL mice. Killed and living BCG, each in doses of 0.008 mg, 0.08 mg, 0.8 mg and 8 mg per mouse, were intravenously inoculated 7 days prior to primary immunization with HRBC. Secondary immunization was carried out 28 days later with TNP-HRBC. Anti-HRBC and anti-TNP antibodies were estimated by a hemagglutination test. The results showed that pretreatment with killed or living BCG enhanced the antibody production against both HRBC and TNP. Comparing the effects of these two BCG preparations, it was noted that killed BCG augmented the anti-HRBC antibody production more effectively than living BCG. In regard to the anti-TNP antibody production, living BCG exhibited a greater augmenting effect than killed BCG. This difference in the modes of action of killed and living BCG was remarkable when two groups given 8 mg of killed and living BCG were compared. In addition, it was shown that living BCG at a dose as high as 8 mg was able to augment the anti-TNP antibody production, even in the absence of preceding immunization with HRBC.

Animals↗
PubMed1978

Mode of immunopotentiating action of BCG: macrophage activation produced by BCG-infection.

Macrophage activation as measured by increased rate of carbon clearance and spreading of peritoneal macrophage was studied in mice infected with BCG, strain Japan. BCG caused marked increase of the numbers of peritoneal cells and spread macrophages. The increases of spread macrophages reached a peak at the 3rd week of BCG infection introduced by the both routes of intravenous(i.v.) injection and foot pad(f.p.) injection. BCG also enhanced the clearance of carbon. In the case of BCG given i.v., the increase of the rate of carbon clearance was biphasic : an early increase reaching maximum at the 1st week and a late increase reaching maximum at the 3rd week of BCG infection. When BCG given into one foot pad, peak increase was reached at the 5th week. The activation of macrophages as measured by increased levels of carbon clearance and increased numbers of spread macrophages in the mice receiving BCG i.v. was approximately two fold greater than that in the mice receiving BCG by f.p. route. When sheep red blood cells (SRBC) as antigen were injected i.v. into the mice primed with BCG i.v., the optimal interval between BCG priming and subsequent antigen injection varied with the dose of antigen for the induction of the highest level of delayed type hypersensitivity (DTH) to SRBC, but not with the degree of macrophage activation.

Animals↗
PubMed1985

[Shared antigens between BCG and tumor cells--immunotherapy with BCG for mouse tumor].

Cytotoxic activity of anti-BCG rabbit serum (A-BCG) and the antigenic relationship between BCG and tumor cells were studies. A-BCG showed high cytotoxic activity against line 10 tumor cells of guinea pig Strain 2 and Colon 26 tumor cells of BALB/c mouse but not to cells of human bladder cancer (HT 1197, HT 1376). Cell-killing activity of A-BCG against line 10 and Colon 26 was dependent on complement participation. It was also found that Colon 26 cells were heterogenous in their susceptibility to the killing activity of A-BCG. Antigenic studies between BCG and tumor cells were undertaken using on indirect immunofluorescence method and it was found that all tumor cells used in the experiment shared common antigens with BCG. In immunotherapy with BCG for Colon 26 tumors, BCG worked effectively for suppressing tumor growth. However, enhancement of tumor growth in some of the BCG-treated mice was observed.

Animals↗