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PubMed1992

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

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 C57BL/10J, showed exceptional susceptibility, and 10(6) amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on which the footpad primary lesion occurred. 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 which reach a discreet peak after 12 weeks, do not heal but do not ulcerate. DBA/2 mice is, therefore, a good model for immunomodulation. 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(6) BCG viable dose and 10 micrograms or 50 micrograms 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.

Adjuvants, Immunologic↗

PubMed1992

[Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group].

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

PubMedDate not supplied

BCG vaccine and post-BCG complications among infants in Gaza Strip, 1999.

The relationship between post-BCG complications and the practices of administration and/or use of certain batches of BCG vaccine was investigated. A questionnaire were given to nurses administering BCG vaccination. An abstraction sheet was used to analyse cases with BCG complications among infants (n = 552) and schoolchildren (n = 97). The rate of complications was 14.7/1000 among infants and 2.5/1000 among schoolchildren in 1997. The complications rate was 19.1/1000 at UNRWA and 8.3/1000 at governmental health services. It was found that a single batch of BCG 2611-11 combined with incorrect administering of the vaccine was responsible for this outbreak of complications. Therefore, the establishment of a surveillance system to monitor adverse events following immunization is needed.

Abscess↗

PubMed1992

[BCG osteoarthritis on knee prosthesis after intra-vesical BCG therapy].

A case of Calmette-Guérin bacillus (BCG) infection of a knee implant during intravesical BCG-therapy is reported. The course was favorable after replacement of the implant and administration of antituberculous agents. This case of septic osteoarthritis due to the BCG is different from cases of reactive polyarthritis reported after intravesical instillations of BCG. It probably resulted from diffusion of the BCG via the bloodstream.

Administration, Intravesical↗

PubMed1967

Lysed BCG vaccines. 1. Observations on optimal conditions for BCG growth and lysis.

As a first step towards the production of a lysed BCG vaccine that would have reduced toxicity and allergenicity and yet be immunogenic, the growth and lysis of BCG bacilli under strictly controlled conditions have been studied.BCG grown in both Dubos and Aldridge liquid media showed an arithmetic linear growth, preceded by a very short logarithmic phase. This suggested that some of the cell population became metabolically inactive at a very early stage, possibly owing to suboptimal conditions of growth.Glycine, lysozyme and lithium chloride initiated lysis of BCG growth in the aforementioned media 24-48 hours after inoculation. After 2 weeks' incubation approximately 50% of the original BCG culture was lysed and the viable count had fallen 1000-fold. The autolytic pattern of BCG in a nitrogen-deficient, chemically defined Aldridge medium is also described.

BCG Vaccine↗

PubMed1984

Suppression of BCG cell wall-induced delayed-type hypersensitivity by pretreatment with killed BCG: induction of nonspecific suppressor T cells by the adjuvant portion (MDP) and of specific suppressor T cells by the antigen portion (TAP).

We showed previously that antigen-nonspecific suppressor T cells induced by i.v. injection of heat-killed bacillus Calmette-Guérin (BCG) were involved in suppression of delayed-type hypersensitivity (DTH). We suggested that the adjuvant portion of BCG might be involved in the induction of these cells. In this report, we show that BCG cell wall-induced DTH responses in mice pretreated with muramyl dipeptide (MDP), a minimum adjuvant constituent of BCG, were suppressed nonspecifically. In addition, we show that pretreatment with tuberculin active peptide (TAP), the antigenic peptide from Mycobacterium tuberculosis, induces antigen-specific suppression of DTH responses. In both instances, suppression was shown to be due to non-adherent cells that act to inhibit elicitation of DTH. Furthermore, using the macrophage migration inhibition assay, an in vitro correlate of DTH, we found that antigen-nonspecific and antigen-specific suppressor T cells were induced by the injection of MDP and TAP, respectively. Thus, suppressor T cells induced by the adjuvant and antigen portions of BCG may act by interfering with the lymphokine-dependent mechanisms by which DTH effector T cells elicit DTH.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1979

Interferon and cytotoxic factor (cytotoxin) released in the blood of mice infected with Mycobacterium bovis BCG. II. Influence of time after BCG inoculation on production of interferon and cytotoxin by capsular polysaccharide of Klebsiella pneumoniae or by bacterial lipopolysaccharide and on hyperreactivity to their lethal effects.

The time course of the occurrence of hyperreactivity in interferon and cytotoxin responses to the active substance (neutral fraction) of the capsular polysaccharide of Klebsiella pneumoniae (neutral CPS-K) and bacterial lipopolysaccharide (LPS) and of the hyperreactivity to their lethal effects was followed after infection with BCG in SMA and ICR strains of mice. The duration of these hyperreactivities of BCG-infected mice depended on the inoculum doses of BCG. The time patterns of the hyperreactivity to the lethal effects of neutral CPS-K and LPS were similar in both strains of mice, although the maximum toxicity of LPS by the intraperitoneal route in BCG-infected mice on a weight basis was stronger than that of neutral CPS-K. Irrespective of inducer and mouse strain, the time pattern of the hyperreactivity to produce cytotoxin was similar to that of the hyperreactivity to produce interferon. The patterns for these phenomena when neutral CPS-K was used as an inducer were also similar to those when LPS was used. In ICR mice the hyperreactivity in interferon and cytotoxin responses to either neutral CPS-K or LPS decayed significantly earlier than the hyperreactivity to their lethal effects, whereas in SMA mice the occurrence of both types of hyperreactivities seemed to be associated. Therefore, it is suggested that the mechanism for the hyperreactivity in interferon and cytotoxin responses to neutral CPS-K or LPS in BCG-infected mice is not necessarily the same as that for the hyperreactivity to their lethal effects.

Animals↗

PubMed1996

A novel method for monitoring Mycobacterium bovis BCG trafficking with recombinant BCG expressing green fluorescent protein.

To better understand intracellular and extracellular trafficking of Mycobacterium bovis bacillus Calmette-Guérin (BCG) when used as an intravesical agent in the treatment of transitional cell carcinoma (TCC) of the bladder, recombinant BCG (rBCG) expressing the jellyfish green fluorescent protein (GFP) was created. When the MB49.1 murine TCC cell line was incubated with GFP-expressing rBCG, internalization of the pathogen could be directly visualized by UV microscopy and quantitated by flow cytometry. The in vitro internalization of the GFP rBCG by the bladder tumor cells was temperature dependent, occurring most readily at 37 degrees C and being severely inhibited at 4 degrees C. Optimum internalization was achieved in vitro at a 10:1 BCG-to-tumor cell ratio over 24 h during which approximately 16% of the tumor cells became infected. Cytochalasin B, a phagocytosis inhibitor, abrogated the ingestion by almost 100% at a concentration of 200 micrograms/ml, indicating that contractile microfilaments likely played an important role in this process. By using mitomycin, a DNA cross-linking reagent, to inhibit proliferation of MB49.1 cells, clearance of about 40% of the green rBCG was achieved by 3 days postinfection. No significant difference between the GFP rBCG and wild-type BCG was observed in the ability to induce the expression of cell membrane proteins of major histocompatibility classes I and II, ICAM-I and -II, B7-1 and -2, of Fas from MB49.1 cells or cytokine production from mouse spleen cells. These results indicate that GFP rBCG may serve as a useful substitute for wild-type BCG in future studies of in vivo trafficking experimental and clinical immunotherapy.

Animals↗

PubMed2006

Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults.

BACKGROUND: Oral administration of BCG was the route initially used by Calmette and Guérin, but was replaced by intradermal administration in virtually all countries after the Lubeck accident. However, Brazil continued to administer oral BCG Moreau RDJ, which was maintained until the mid-1970s when it was substituted by the intradermal route. Although BCG vaccination has been used in humans since 1921, little is known of the induced immune response. The aim of this study was to analyse immunological responses after oral vaccination with M. bovis BCG Moreau RDJ. METHODS: This study in healthy volunteers has measured cellular and humoral aspects of the immunological response to oral M. bovis BCG Moreau RDJ in Rio de Janeiro, Brazil. T-cell trafficking and Th1 and Th2 cytokine responses are described, as well as isotype-specific antibody production using novel techniques. RESULTS: Oral immunisation has no adverse effects. We have shown that there are cellular and humoral immunological responses after oral immunisation. Oral revaccination does not induce a positive skin test in responsive individuals and multiple booster orally was able to induce modulation in humoral immunological responses (switch from IgG to IgA) in previously immunised subjects and incapable of inducing tolerance. In contrast, the cellular immune response does not differ between vaccinated individuals with positive and negative skin test reactions. CONCLUSION: All subjects, including those who did not respond to the skin test at study commencement, were capable of mounting humoral and cellular immune response to the antigens tested.

Journal Article↗

PubMed1991

Diagnostic value of measuring BCG sonicate antigen and anti-BCG antibodies in the cerebrospinal fluid and blood of patients with tuberculous meningitis.

Fourteen cerebrospinal fluid (CSF) and paired blood samples were obtained from patients with tuberculous meningitis, seven with positive culture and seven clinical/laboratory diagnosis. Another 14 paired specimens served as control, including 7 infectious meningitis and 7 non-inflammatory neurological diseases. Four groups were thus classified, including confirmed and suspected patients, and controls with infectious meningitis and neurological diseases. Measurements of Bacillus Calmette-Guérin (BCG) sonicate antigen and IgG antibody were performed using enzyme-linked immunosorbent assay. Generally, CSF BCG sonicate antigen level and anti-BCG sonicate antibody of patients with tuberculosis meningitis were higher than in control groups; greater antigen levels were found in confirmed patients than in non-inflammatory subjects (p less than 0.05), and in suspected patients than in infectious and non-inflammatory subjects (p less than 0.05 and p less than 0.01). For serum anti-BCG sonicate levels, confirmed patients had higher antibody value than non-inflammatory subjects (p less than 0.05). To conclude, detection of high levels of both BCG sonicate antigen and antibody in CSF and blood samples shows great value in the diagnosis of tuberculous meningitis. However, given the limited samples of the current research, more data are needed to elucidate the sensitivity and specificity of such tests.

Adolescent↗

PubMed1981

BCG, Corynebacterium parvum or Mycobacterium leprae added to cultures of BCG-primed mouse spleen cells cause an enhanced primary antibody response in vitro.

A few weeks after mice were injected i.v. with 10(8) live Mycobacterium bovis, BCG, the antibody response of their spleen cells to SRBC in vitro was comparable with the response of cells from untreated mice. Addition of BCG organisms to the culture vessels resulted in enhanced antibody-forming cell (AFC) responses by the primed cells but not by the cells from the untreated mice. No evidence was found for a direct stimulation of B cells and cell depletion experiments suggested macrophages were directly involved. BCG added to the cultures up to 68 h after they were set up, but not later, still caused enhancement. No enhancement was found when DNP-Ficoll was used as antigen. The ability to stimulate the anti-SRBC response was not restricted to the organism used for priming. Enhancement was also found if C. parvum or M. leprae were added to BCG-primed cells and if BCG was added to C. parvum-primed cells. The relevance of the results to the search for a leprosy vaccine is discussed.

Animals↗

PubMed1979

Adjuvant immunotherapy of lung cancer with BCG cell wall skeleton (BCG-CWS).

Four hundred fifty-five patients with lung cancer were treated with oil-attached cell-wall skeleton of bacillus Calmette-Guérin (BCG-CWS) as adjuvant immunotherapy following initial conventional therapy. The overall survival period of the patients was prolonged significantly as compared with that of 380 patients in a historical control group receiving initial conventional therapy alone (p less than 0.0001). The prolongation of the survival period of the patients was also statistically significant when classified according to clinical stages and histological cell types. The therapeutic effect was remarkable in patients combined with malignant pleurisy. Intrapleural injection of BCG-CWS resulted in not only prevention of accumulation of pleural effusion and abrogation of tumor cells but also in prolongation of survival period (P = 0.016). No serious side effects due to BCG-CWS were experienced. From the previous experimental studies and clinical experiences with human tumors, it can be concluded that adjuvant immunotherapy with BCG-CWS is a useful therapeutic modality for lung cancer, especially in cases combined with malignant pleurisy.

Adenocarcinoma↗

PubMed1980

Augmentation of immunity of line 10 hepatoma by BCG: comparison of different BCG preparations.

The line 10 hepatoma of strain 2 guinea pigs was used in order to evaluate the adjuvant efficacy of eight Bacillus Calmette-Guérin (BCG) suspensions which differed in strain, method of preservation, or dosage. Lyophilized Tice BCG was consistently the most effective preparation. Each strain had adjuvant activity in at least one experiment. The method of preservation of BCG (fresh-frozen vs. lyophilized) did not have a consistent, a predictable influence on adjuvanticity. A ten-fold increase in the dosage of BCG or of the whole vaccine was not supraoptimal.

Adjuvants, Immunologic↗

PubMed1993

A randomised prospective study comparing intravesical instillations of mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 tumours and primary carcinoma in situ of the urinary bladder. Dutch South-East Cooperative Urological Group.

We compared intravesical instillations with mitomycin-C (MMC), Bacillus Calmette-Guerin (BCG) Tice, and BCG-RIVM in patients with pTa-pT1 papillary carcinoma and primary carcinoma in situ (CIS) of the bladder. Nine instillations with MMC were given or 6 weekly instillations with BCG. Early recurrences were treated with additional instillations. For toxicity and efficacy 437 patients were evaluated with a median follow-up of 32 months (range 12-56). Drug-induced and bacterial cystitis were the most frequent side-effects. The number and severity of side-effects (chi 2 test) were comparable in both BCG groups, but were significantly less in the MMC group for drug-induced cystitis (P = 0.009), other local side-effects (P = 0.004) and systemic side-effects (P < 0.001). The disease-free percentage (log-rank test) showed no significant difference for the three arms for papillary tumours (P = 0.08), nor the CIS (P = 0.20), although for CIS numbers are small. Additional instillations did not influence toxicity or efficacy.

Administration, Intravesical↗

PubMed1993

Six years' experience with the discontinuation of BCG vaccination. 2. Cost and benefit of mass BCG vaccination.

In 1986 the compulsory mass BCG vaccination of infants born in a selected area of the Czech Republic was abolished. The observed annual risk of tuberculous infection in children aged 0-6 years was below 0.1% and the annual risk of tuberculous disease 7/100,000. The increase of tuberculous cases among nonvaccinated children indicated a protective efficacy of BCG vaccine of 80%. A benefit analysis proved that the advantages and disadvantages of BCG vaccination were in balance. The number of nonvaccinated children developing tuberculosis was so small that mass application of BCG has been found to be redundant. The important advantage of not using the vaccination is the maintenance of the epidemiological and diagnostic value of tuberculin tests. The tests in connection with preventive chemotherapy remain an important tool, enabling control of infected individuals.

BCG Vaccine↗

PubMed1994

Serological analysis by A60 antigen ELISA and BCG immunoblotting in domestic carnivores experimentally vaccinated with mycobacterium bovis BCG.

The serological response to Mycobacterium bovis BCG vaccination was studied in 3 cats, 3 dogs and 3 puppies. The animals received two doses of 0.1 mg of BCG and were studied over a period of 8 months simultaneously by ELISA with antigen A60 (Anda Biologicals, Strasbourg, France) and immunoblotting with BCG. The two methods detected an increase of antibodies at 3 or 5 weeks. In the cats, specific antibody titer remained high and stable for more than one year, in the dogs they diminished quickly within 23 weeks. Carnivores elicit a serological response against specific protein antigens in the bands corresponding to 18 and 25kDa, 30 and 45kDa, and especially 35 and 42kDa bands, and to minor bands at higher molecular weight. Non-specific bands at 50-55 kDa and 70 kDa, assigned to heat shock proteins, were enhanced by BCG vaccination. Cat immunosera recognized on A60 immunoblots the specific homologous bands at 20-25 kDa and 32 kDa, but also two other dominant bands: one was partially specific (65 kDa) and the other was absent from the M. bovis and M. paratuberculosis profiles. The suitability of A60 ELISA for detection of mycobacterial infection in carnivores may be highlighted by immunoblot analysis.

Animals↗

PubMed2002

BCG septicemia after radical cystectomy: a rare postoperative complication following BCG therapy.

It is reported a case of life-threatening septic shock due to BCG septicemia after radical cystectomy in a patient with a previous treatment with BCG therapy. In the absence of response to standard antimicrobial therapy and a negative CT scan, a PCR-based technique detected the presence of BCG bacilli in bloodstream. Immediate antimycobacterial therapy resolved the sepsis, thus suggesting either the awareness of this infection or the prompt antimycobacterial therapy as the key for the appropriate management. Furthermore, isoniazid prophylaxis should be taken into consideration in patients with history of intravesical BCG therapy undergoing cystectomy.

Aged↗

PubMedDate not supplied

[BCG-vaccination in neonates as a cause of osteomyelitis--an argument against BCG-vaccination?].

BCG-osteomyelitis is a rare complication of BCG-vaccination. By means of a case report clinical and immunological findings are discussed. Contrary to the undramatic clinical symptoms the x-ray showed pronounced osteolytic lesions in the sternum. The bacteriological examination demonstrated mycobacteria of BCG-type. Immunological investigations presented normal humoral and cellular immunity. The therapy (curettage, antituberculous drugs) was effective. In spite of this complication the BCG-vaccination is furthermore recommended.

BCG Vaccine↗