Randomized Controlled Trial of<i>Mycobacterium vaccae</i>Immunotherapy in Non–Human Immunodeficiency Virus–Infected Ugandan Adults with Newly Diagnosed Pulmonary Tuberculosis

Johnson, John L.; Kamya, R. Moses; Okwera, Alphonse; Loughlin, Anita M.; Nyole, Sam; Hom, David L.; Wallis, Robert S.; Hirsch, Christina S.; Wolski, Kathy; Foulds, John; Mugerwa, Roy D.; Ellner, Jerrold J.

doi:10.1086/315393

Cited by 75 publications

(40 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Asthmatic volunteers received a single intradermal injection of SRL172, a preparation containing 1610 9 (1 mg) heat-killed M. vaccae (SRL172) has been used in previous clinical studies involving patients with pulmonary tuberculosis [12], melanoma [13], cancers of the prostate [14] and cancer of the lung [15,16], where the aim has been to promote Th1 cytokine-dependent immune defences. Following observations that M. vaccae suppresses established IL-5 and IgE synthesis in ovalbumin-sensitised mice [17] and evokes regulatory T-cells that downregulate Th2 responses [18], it was further hypothesised that it may be able to reduce Th2 responses not only in developing allergic disease but also in chronic adult asthma.…”

mentioning

confidence: 99%

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Camporota¹,

Corkhill²,

Long³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

T-helper (Th)2 cytokines play a central role in asthma. Therefore, a double-blind randomised study was conducted to investigate whether heat-killed Mycobacterium vaccae (SRL172), a potent downregulator of Th2 cytokines, can reduce allergen-induced airway responses in patients with atopic asthma.A total 24 male asthmatics participated in this study. A bronchial allergen challenge was performed along with early (EAR) and late asthmatic responses (LAR) 2 weeks before and 3 weeks after a single intradermal injection of SRL172 or placebo. Before and after treatment, serum immunoglobulin (Ig)E levels and in vitro production of interleukin (IL)-5 by peripheral blood lymphocytes were studied.Neither treatment affected the EAR. SRL172 caused a mean 34% reduction of the area under the curve of the forced expiratory volume in one second (FEV1) changes during the LAR, which failed to reach conventional statistical significance when compared with placebo. SRL172 also caused a mean 25% decrease in the maximum fall in FEV1 during LAR, but this was not significantly different from placebo. SRL172 caused a reduction in serum IgE and IL-5 synthesis in vitro 3 weeks post-treatment (p=0.07).This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed.

show abstract

mentioning

confidence: 99%

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Camporota¹,

Corkhill²,

Long³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…45 Different from an earlier therapeutic TB vaccine candidate SRL-172, the primary component of which was also inactivated M. obuense, DAR-901 is grown broth rather than agar, a more scalable production method. [45][46][47] Recently, a Phase I trial of DAR-901, is currently conducted in HIV negative and HIV positive adults previously vaccinated with BCG to assess the safety, tolerability, and immunogenicity of multiple doses of DAR-901 at different dose levels. Further clinical trials need to be performed to determine the role of DAR-901 in the prevention of TB infection among children.…”

Section: Dar-901mentioning

confidence: 99%

Current status of new tuberculosis vaccine in children

Pang

Zhao

Cohen³

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

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.

show abstract

“…They recommended applying the immune-treatment with M. vaccae at the beginning of the chemo-treatment, on newly diagnosed patients [49,50]. The clinical trial in Durban [51] that crucified this approach was conducted on newly diagnosed patients under chemotherapy with 4 drugs.…”

Section: Immunotherapymentioning

confidence: 99%

Can the Triumphant March of TB be Stopped? A Critical Appraisal of the Currently Applied Policy of Eradication

Maes¹

2016

Clin Microbiol

View full text Add to dashboard Cite

The fight against TB is organized by International (WHO, International Union of Tuberculosis and Lung Diseases (UTLD) and National organizations (Ministries of Health). Their strategy is based on a "herd medicine" approach. The vaccine and the massive administration of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide-with streptomycin eventually added for the resistant cases) worldwide during decennia were expected to solve the TB problem. They did not because the means applied to fight the disease were not appropriate. The BCG vaccine is the only vaccine in use, yet it sometimes promotes TB multiplication instead of eradication; only four drugs were imposed by Standard Operating Procedures during decennia, of which some are immunodepressive and may, under some conditions, add to the immunodepressive activity of the pathogen and favour relapse; the diagnosis limited to the detection of the pathogen ignores the immune condition of the patients under treatment.The prognosis, diagnosis and treatment of tuberculosis can be improved. The BCG vaccine is iatrogenic and needs replacement; diagnostic tests based on the detection of the pathogen have their use but need to be completed with the detection of asymptomatic cases and the monitoring of the immune status of the treated patients with a sero-diagnostic test that detects unapparent infections and immune-depressed cases; the drugs used to fight TB must be re-evaluated and complemented by the application of immune-stimulating products to those refractory patients who show a need therefore. The continuing use of an iatrogenic vaccine and of immunodepressive drugs defeats the purpose.

show abstract

Randomized Controlled Trial ofMycobacterium vaccaeImmunotherapy in Non–Human Immunodeficiency Virus–Infected Ugandan Adults with Newly Diagnosed Pulmonary Tuberculosis

Cited by 75 publications

References 38 publications

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Current status of new tuberculosis vaccine in children

Can the Triumphant March of TB be Stopped? A Critical Appraisal of the Currently Applied Policy of Eradication

Contact Info

Product

Resources

About