scholarly journals IL-10 receptor blockade delivered simultaneous with BCG vaccination sustains long term protection against Mycobacterium tuberculosis infection in mice

2021 ◽  
Author(s):  
Varun Dwivedi ◽  
Shalini Gautam ◽  
Colwyn A. Headley ◽  
Tucker Piergallini ◽  
Jordi B Torrelles ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Vaccination Strategy ◽  
Interleukin 10 ◽  
Vaccine Strategy ◽  
Mycobacterium Tuberculosis Infection ◽  
Bcg Vaccination ◽  
Alternative Approach ◽  
Cytokine Levels ◽  
Single Vaccination

Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunization still remains the best vaccination strategy available to control the development of active tuberculosis (TB). Protection afforded by BCG vaccination gradually wanes over time and while booster strategies have promise, they remain under development. An alternative approach is to improve BCG efficacy through host-directed therapy. Building upon prior knowledge that blockade of interleukin-10 receptor 1 (IL-10R1) during early Mycobacterium tuberculosis (M.tb) infection improves and extends control of M.tb infection in mice, we employed a combined anti-IL-10R1/BCG vaccine strategy. A subcutaneous, single vaccination of BCG/αIL10-R1 increased the numbers of CD4+ and CD8+ central memory T cells, and reduced TH1 and TH17 cytokine levels in the lung for up to 7 weeks post vaccination. Subsequent M.tb challenge in mice showed both an early (4 week) and sustained long-term (47 week) control of infection, which was associated with increased survival. In contrast, protection of BCG/saline vaccinated mice waned 8 weeks post M.tb infection. Our findings demonstrate that a single and simultaneous vaccination with BCG/αIL10-R1 sustains long-term protection, identifying a promising approach to enhance and extend the current BCG mediated protection against TB.

scholarly journals Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda

2016 ◽  
Vol 72 (3) ◽  
pp. 344-352 ◽  
Author(s):  
Violette Dirix ◽  
Kinda Schepers ◽  
Marguerite Massinga-Loembe ◽  
William Worodria ◽  
Robert Colebunders ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculosis Infection ◽  
Added Value ◽  
Cytokine Release ◽  
Mycobacterium Tuberculosis Infection

Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study

The Lancet ◽  
2005 ◽  
Vol 366 (9495) ◽  
pp. 1443-1451 ◽  
Author(s):  
Ahmet Soysal ◽  
Kerry A Millington ◽  
Mustafa Bakir ◽  
Davinder Dosanjh ◽  
Yasemin Aslan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Community Based ◽  
Bcg Vaccination

scholarly journals THE EFFECT OF ALPHA-MANGOSTIN IN BALANCING THE RATIO OF CYTOKINES PRO-AND ANTI-INFLAMMATION-GAMMA (IFN-γ/IL-10) AND SEVERITY OF THE DISEASE IN MICE INFECTED WITH MYCOBACTERIUM TUBERCULOSIS MULTIDRUG-RESISTANT

2016 ◽  
Vol 9 (9) ◽  
pp. 273
Author(s):  
Dyan Kunthi Nugrahaeni ◽  
Suharyo Hadisaputro ◽  
Ari Suwondo ◽  
Edi Dharmana
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Interleukin 10 ◽  
Multidrug Resistant ◽  
Interferon Γ ◽  
Control Group ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Severity Of The Disease ◽  
And Control ◽  
Anti Inflammation

ABSTRACTObjective: The objective of this study was observed to measure the effect of alpha-mangostin in balancing the ratio of interferon-gamma (IFN-γ) andinterleukin-10 (IL-10), and the severity of the disease in mice which infected with Mycobacterium tuberculosis multidrug-resistant (TB-MDR).Method: Infected BALB/c mice were consisted of five groups: Treated with anti-TB drugs+α-mangostin, treated with anti-TB drugs, given α-mangostinduring treatment, and control group. Cytokine levels of culture supernatant of spleen cells were measured by enzyme-linked immunosorbent assay.The number of bacterial colonies was derived from a primary cell culture of bronchoalveolar lavage. Statistical analysis was performed with Anova,Kruskal-Wallis test and correlation Pearson, and Spearman-rank test.Result: Median IFN-γ production was higher in mice, which given with α-mangostin during treatment is 1838.2 pg/ml and control is 1585.5 pg/mlcompared treated with anti-TB drugs+α-mangostin (1312 pg/ml) and anti-TB drugs (1429.3 pg/ml) (p>0.05). The highest result production of medianIL-10 in the 3th group is (465.91 pg/ml) and the lowest in the control group is 195.29 pg/ml, p>0.05. Median IFN-γ/IL-10 ratio of the 3th group verylow (3.94), it means the 3th group is experienced with severity of TB. Alpha-mangostin was decreased in severity of disease based on the number ofTB-MDR bacterial colonies (p≤0.05).Conclusion: α-mangostin have an effect on the balancing IFN-γ/IL-10 ratio and reduce a severity of TB-MDR with using immunomodulator.Keywords: Tuberculosis multidrug-resistant, Alpha-mangostin, Interferon-γ/interleukin-10 ratio, Number of tuberculosis multidrug-resistantbacterial colonies.

scholarly journals Effectiveness of BCG Vaccination Against Mycobacterium tuberculosis Infection in Adults: A Cross-sectional Analysis of a UK-Based Cohort

2019 ◽  
Vol 221 (1) ◽  
pp. 146-155 ◽  
Author(s):  
Anthea L Katelaris ◽  
Charlotte Jackson ◽  
Jo Southern ◽  
Rishi K Gupta ◽  
Francis Drobniewski ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Vaccine Development ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Cross Sectional ◽  
Bcg Vaccination ◽  
Cross Sectional Analysis ◽  
Vaccination History ◽  
Sectional Analysis

Abstract Background BCG appears to reduce acquisition of Mycobacterium tuberculosis infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of M. tuberculosis infection in adults. Methods We conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression. The effects of age at BCG and time since vaccination were also explored. Results Of 3453 recent tuberculosis contacts, 27.5% had LTBI. There was strong evidence of an association between BCG and LTBI (adjusted odds ratio = 0.70; 95% confidence interval, .56–.87; P = .0017) yielding a VE of 30%. VE declined with time since vaccination but there was evidence that LTBI prevalence was lower amongst vaccinated individuals even >20 years after vaccination, compared with nonvaccinated participants. Conclusions BCG is associated with lower prevalence of LTBI in adult contacts of tuberculosis. These results contribute to growing evidence that suggests BCG may protect against M. tuberculosis infection as well as disease. This has implications for immunization programs, vaccine development, and tuberculosis control efforts worldwide. Clinical trials registration NCT01162265.

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