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Limitations of the BCG vaccine and new prophylaxis strategies against human tuberculosis

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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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... 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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... 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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