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BCG (Bacille Calmette Guérin), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine against tuberculosis. Notwithstanding its protection of children, BCG has failed to protect adults against active pulmonary tuberculosis, especially in countries where the disease is endemic. Any new tuberculosis vaccine should protect several categories of people, including children, adults, the elderly and immunodeppressed patients. An important feature is immunization safety for all of these classes. The aim of this review is to describe new vaccination strategies, such as subunit vaccines, DNA vaccines, vaccines with live microorganisms and vectors, and to discuss the application of these new strategies for the control and eradication of tuberculosis.
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... 6 BCG is the only vaccine that is licensed to control the incidence of TB, especially for combating extrapulmonary TB in children such as tuberculous meningitis and miliary TB. 7 Nevertheless, the vaccine efficacy has come under question as, despite the global vaccination protocol, developed as well as developing countries report an increase in the number of TB cases. 6,8 High variability of efficacy and low protection against pulmonary TB has put the BCG vaccine under constraint and thus, WHO considered the development and implementation of new TB vaccines to be a priority. 4,8 Several promising candidates have been proposed, and among them, subunit vaccines are the most promising since they can overcome safety concerns and optimize antigen targeting; however, to increase immunogenicity, decrease the needed antigen dose, ensure targeted delivery, and optimize the antigens' delivery and interaction with the immune cells, adjuvants is a prerequisite. ...
... 6,8 High variability of efficacy and low protection against pulmonary TB has put the BCG vaccine under constraint and thus, WHO considered the development and implementation of new TB vaccines to be a priority. 4,8 Several promising candidates have been proposed, and among them, subunit vaccines are the most promising since they can overcome safety concerns and optimize antigen targeting; however, to increase immunogenicity, decrease the needed antigen dose, ensure targeted delivery, and optimize the antigens' delivery and interaction with the immune cells, adjuvants is a prerequisite. 8 It is well known that the body's defense against M. tuberculosis infection is related to the development and production of M. tuberculosis-specific multifunctional Th1type T-cell subsets, in collaboration with the stimulation of macrophages, thereby inhibiting mycobacterial replication during the early infection phase. ...
... 4,8 Several promising candidates have been proposed, and among them, subunit vaccines are the most promising since they can overcome safety concerns and optimize antigen targeting; however, to increase immunogenicity, decrease the needed antigen dose, ensure targeted delivery, and optimize the antigens' delivery and interaction with the immune cells, adjuvants is a prerequisite. 8 It is well known that the body's defense against M. tuberculosis infection is related to the development and production of M. tuberculosis-specific multifunctional Th1type T-cell subsets, in collaboration with the stimulation of macrophages, thereby inhibiting mycobacterial replication during the early infection phase. 9 An aim of the TB vaccine design is determination of antigens-stimulating protective T-cell subsets at the early stage of infection. ...
Article
This study attempted to explore the immunogenicity of chitosan nanoparticles containing fusion protein (Hspx–PPE44–EsxV; HPE) and resiquimod adjuvant (HPERC) in BALB/c mice. HPE was initially expressed in E. coli BL21 cells. HPE and resiquimod adjuvant were then encapsulated in chitosan nanoparticles (HPERC). One group of mice were subcutaneously vaccinated on days 0, 14, and 28 with HPERC, and the other group was primed with bacilli Calmette-Guérin (BCG) on day 0 and then boosted with HPERC on days 14 and 28. Two weeks after the last injection, IFN-γ, IL-4, and IL-17 in spleen cell culture supernatants, and IgG2a and IgG1 titers in sera were measured. HPERC size was 130.84 ± 12.08 nm ( n = 5). Zeta potential of HPERC was 29 ± 4 mv. The highest IFN-γ concentration was detected in BCG-primed mice that were boosted with HPERC. In addition, IL-17 production was significantly increased in all groups compared with that of control, except in those that received nanoparticle (NP), adjuvant (ADJ), NP/ADJ, and fusion protein (Hspx–PPE44–EsxV) (HPE). Comparison of IFN-γ and IL-4 concentration determined that Th1 was activated in BCG-primed and HPERC-boosted group in comparison to the other groups. No significant difference in concentration of IL-4 was observed between groups receiving HPERC and BCG-primed and HPERC-boosted group in comparison to group BCG. Concentrations of IgG2a and IgG1 also increased compared to the control group and the rate of IgG2a was higher compared to IgG1. Chitosan containing HPERC vaccine could induce a high level of specific cytokines in mice. The group of mice which first received BCG and then HPERC as booster vaccine could produce significant amounts of IFN-γ, IL-17, and IgG2a.
... Tuberculous familial contours of children have often been reported [7,8]. Almost all children had been vaccinated with BCG, thus demonstrating already the limits of this vaccine in the prevention of tuberculosis [9,10]. Factors favoring infection such as passive smoking reported by other authors [11], as well as malnutrition have been found in some of our patents. ...
... Although BCG is a low-cost and widely used vaccine, its efficacy has widely varied in clinical assays-values ranged from 0 to 80%. Notwithstanding its protection of children, BCG has failed to protect adults against active pulmonary tuberculosis, especially in countries where the disease is endemic 14 . Despite the prior vaccination with BCG, a positive QFT-GIT in a child having close contact with infectious adult most likely represents LTBI and there should be consideration for treatment of LTBI, especially if the child is younger than 5 years. ...
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Background: Latent tuberculosis infection (LTBI) represents a substantial public health burden. This study was conducted to determine the frequency of LTBI in children by using Quanti FERON-TB Gold in-tube test (QFT-GIT) in children less than 12 years of age in a tertiary care centre, Lahore Methods: This cross-sectional study was conducted in the Department of Pediatrics, King Edward Medical University, Lahore, Pakistan, from July 2014 to June 2015. By non-probability convenient sampling, 250 children having contact with a confirmed (sputum positive adult case of pulmonary TB) or suspected tuberculosis case (adult having fever and unremitting cough for 3 weeks) were included in the study. Presence or absence of BCG vaccination scar was documented. Diagnosed cases of TB were excluded. All children were subjected to QFT-GIT for evidence of LTBI. Each child was treated according to the individual merit (prophylaxis was offered to positive cases). Data were analyzed by SPSS 20.0 mean for continuous variables and frequencies for categorical variables were used to summarize the data. Results: A total of 250 children under 12 years were enrolled. Mean age was 6.48 ± 2.97 years. Among 250, 136 (54.4%) were male and 114 (45.6%) were female. Out of 250, 75 (30%) of children were found to be positive QFT-GIT test. When data was analyzed for BCG scar and QFT-GIT positivity, it was found that 8.4% vaccinated male & 10% vaccinated female were affected, whereas 17.6% of children less than 5 years were having LTBI. Conclusion: The frequency of latent tuberculosis infection in children less than 12 years of age is 30%. It is need of time to screen each child for LTBI who has close contact with adult case of TB in developing countries like Pakistan.
... Increasing resistance to anti-tuberculosis drugs has driven the urge for developing new drugs. Prophylactic BCG vaccine failed to reduce the prevalence of infection in adults in the countries where the disease is endemic [2]. Most available ant mycobacterial drugs do not act upon latent forms of Bacillus. ...
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Tuberculosis is the second leading cause of death worldwide. The researchers still finding way to eradicate TB. There is an urgent need to discover new drug which is more effective and less toxic to combat drug resistance. This article reports potential of ES-31 antigen as a new drug target. The characterization of ES-31 antigen showed that ES-31 is a 31 kDa protein antigen and has serine protease as well as lipase activities and shown to be a chymotrypsin-like protein which is having catalytic triad responsible for both activities. Addition of serine protease inhibitors (53-76%), metallo protease inhibitor (46-61%), lipase inhibitor (61%) or anti-ES-31 serine protease antibody (89%) strongly inhibited the MTB H37Ra growth in axenic culture. The importance of excretory secretory ES-31 antigen for the survival of MTB H37Ra and H37Rv bacilli has been shown by 77% and 78% growth inhibition in macrophage culture by protease inhibitor pefabloc. Inhibition of ES-31 leads to growth inhibition of MTB bacilli, suggests that it may be an important drug target for exploring new drugs for tuberculosis.
... Although these figures are alarming, only 5%-10% of those individuals will progress to active disease. 1,2 The majority of the individuals are latently infected as defined by the tuberculin skin test (TST). 3 Purified protein derivative (PPD) is intradermally injected in the forearm of individuals, and after 48 hours, the swelling in response to the crude antigenic cocktail is measured. ...
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Due to several limitations of the only available BCG vaccine to generate adequate protective immune responses, it is important to develop potent and cost-effective vaccines against tuberculosis (TB). In this study, we have used an immune-informatics approach to identify potential peptide based vaccine targets against TB. The proteome of Mycobacterium tuberculosis (Mtb), the causative agent of TB, was analyzed for secretory or surface localized antigenic proteins as potential vaccine candidates. The T- and B-cell epitopes as well as MHC molecule binding efficiency were identified and mapped in the modelled structures of the selected proteins. Based on antigenicity score and molecular dynamic simulation (MD) studies two peptides namely Pep-9 and Pep-15 were analyzed, modelled and docked with MHC-I and MHC-II structures. Both peptides exhibited no cytotoxicity and were able to induce proinflammatory cytokine secretion in stimulated macrophages. The molecular docking, MD and in-vitro studies of the predicted B and T-cell epitopes of Pep-9 and Pep-15 peptides with the modelled MHC structures exhibited strong binding affinity and antigenic properties, suggesting that the complex is stable, and that these peptides can be considered as a potential candidates for the development of vaccine against TB.
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Tuberculosis still remains a huge global health problem. Control of tuberculosis expansion is very difficult. It requires the long-term use of anti-mycobacterial drugs. The Bacille Calmette-Guérin (BCG) vaccination protects against tuberculosis-related meningitis and disseminated tuberculosis. Although vaccination with BCG is considered safe, adverse regional (BCG-itis) and disseminated (BCG-osis) diseases preferentially occur in the immunocompromised host. The infection with human immunodeficiency virus (HIV) by mother-to-child transmission leads to impaired cellular immune responses, a situation that poses a great challenge regarding the universal use of BCG vaccine. World Health Organization recommends that children who are known to be HIV -infected, even if asymptomatic, should no longer be immunized with BCG. We report a patient with solitary skin lesion from the BCG injection site.
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