Displaying publications 1 - 20 of 33 in total

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  1. Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells
    Noh LM, Hussein SH, Sukumaran KD, Rose I, Abdullah N
    J Clin Lab Immunol, 1991 Jun;35(2):89-93.
    PMID: 1688166
    A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.
    Matched MeSH terms: Tuberculosis/immunology
  2. Fulltext Selection of phage-displayed human antibody fragments specific for CD1b presenting the Mycobacterium tuberculosis glycolipid Ac2SGL
    Camacho F, Sarmiento ME, Reyes F, Kim L, Huggett J, Lepore M, et al.
    Int J Mycobacteriol, 2016 06;5(2):120-7.
    PMID: 27242221 DOI: 10.1016/j.ijmyco.2015.12.002
    OBJECTIVE/BACKGROUND: The development of new tools capable of targeting Mycobacterium tuberculosis (Mtb)-infected cells have potential applications in diagnosis, treatment, and prevention of tuberculosis. In Mtb-infected cells, CD1b molecules present Mtb lipids to the immune system (Mtb lipid-CD1b complexes). Because of the lack of CD1b polymorphism, specific Mtb lipid-CD1b complexes could be considered as universal Mtb infection markers. 2-Stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-α-α'-d-trehalose (Ac2SGL) is specific for Mtb, and is not present in other mycobacterial species. The CD1b-Ac2SGL complexes are expressed on the surface of human cells infected with Mtb. The aim of this study was to generate ligands capable of binding these CD1b-Ac2SGL complexes.

    METHODS: A synthetic human scFv phage antibody library was used to select phage-displayed antibody fragments that recognized CD1b-Ac2SGL using CD1b-transfected THP-1 cells loaded with Ac2SGL.

    RESULTS: One clone, D11-a single, light-variable domain (kappa) antibody (dAbκ11)-showed high relative binding to the Ac2SGL-CD1b complex.

    CONCLUSION: A ligand recognizing the Ac2SGL-CD1b complex was obtained, which is a potential candidate to be further tested for diagnostic and therapeutic applications.

    Matched MeSH terms: Mycobacterium tuberculosis/immunology*; Tuberculosis/immunology*
  3. Fulltext Protective effect of a lipid-based preparation from Mycobacterium smegmatis in a murine model of progressive pulmonary tuberculosis
    García Mde L, Borrero R, Lanio ME, Tirado Y, Alvarez N, Puig A, et al.
    Biomed Res Int, 2014;2014:273129.
    PMID: 25548767 DOI: 10.1155/2014/273129
    A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology
  4. Immunoinformatics study on highly expressed Mycobacterium tuberculosis genes during infection
    Nguyen Thi le T, Sarmiento ME, Calero R, Camacho F, Reyes F, Hossain MM, et al.
    Tuberculosis (Edinb), 2014 Sep;94(5):475-81.
    PMID: 25034135 DOI: 10.1016/j.tube.2014.06.004
    The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology; Tuberculosis/immunology
  5. Fulltext In Silico identification of M. TB proteins with diagnostic potential
    Calero R, Mirabal M, Bouza J, Guzmán MV, Carrillo H, López Y, et al.
    BMC Immunol, 2013;14 Suppl 1:S9.
    PMID: 23458073 DOI: 10.1186/1471-2172-14-S1-S9
    TB, caused by Mycobacterium tuberculosis (MTB), is one of the major global infectious diseases. For the pandemic control, early diagnosis with sensitive and specific methods is fundamental. With the advent of bioinformatics' tools, the identification of several proteins involved in the pathogenesis of TB (TB) has been possible. In the present work, the MTB genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits based on the release of cytokines. Seven proteins from the MTB proteome and some of their combinations suited the computational test and the results suggested their potential use for the diagnosis of infection in the following population groups: Cuba, Mexico, Malaysia and sub-Saharan Africa. Our predictions were performed using public bioinformatics tools plus three computer programs, developed by our group, to facilitate information retrieval and processing.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology*; Tuberculosis/immunology
  6. Tuberculosis vaccine candidates based on mycobacterial cell envelope components
    Sarmiento ME, Alvarez N, Chin KL, Bigi F, Tirado Y, García MA, et al.
    Tuberculosis (Edinb), 2019 03;115:26-41.
    PMID: 30948174 DOI: 10.1016/j.tube.2019.01.003
    Even after decades searching for a new and more effective vaccine against tuberculosis, the scientific community is still pursuing this goal due to the complexity of its causative agent, Mycobacterium tuberculosis (Mtb). Mtb is a microorganism with a robust variety of survival mechanisms that allow it to remain in the host for years. The structure and nature of the Mtb envelope play a leading role in its resistance and survival. Mtb has a perfect machinery that allows it to modulate the immune response in its favor and to adapt to the host's environmental conditions in order to remain alive until the moment to reactivate its normal growing state. Mtb cell envelope protein, carbohydrate and lipid components have been the subject of interest for developing new vaccines because most of them are responsible for the pathogenicity and virulence of the bacteria. Many indirect evidences, mainly derived from the use of monoclonal antibodies, support the potential protective role of Mtb envelope components. Subunit and DNA vaccines, lipid extracts, liposomes and membrane vesicle formulations are some examples of technologies used, with encouraging results, to evaluate the potential of these antigens in the protective response against Mtb.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology
  7. Fulltext Role of Interferons in the Development of Diagnostics, Vaccines, and Therapy for Tuberculosis
    Chin KL, Anis FZ, Sarmiento ME, Norazmi MN, Acosta A
    J Immunol Res, 2017;2017:5212910.
    PMID: 28713838 DOI: 10.1155/2017/5212910
    Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology; Tuberculosis/immunology*
  8. Fulltext A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors
    Camacho F, Moreno E, Garcia-Alles LF, Chinea Santiago G, Gilleron M, Vasquez A, et al.
    Front Immunol, 2020;11:566710.
    PMID: 33162982 DOI: 10.3389/fimmu.2020.566710
    Lipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac2SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac2SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac2SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac2SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac2SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac2SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology*
  9. Human tuberculosis and Mycobacterium tuberculosis complex: A review on genetic diversity, pathogenesis and omics approaches in host biomarkers discovery
    Kanabalan RD, Lee LJ, Lee TY, Chong PP, Hassan L, Ismail R, et al.
    Microbiol Res, 2021 May;246:126674.
    PMID: 33549960 DOI: 10.1016/j.micres.2020.126674
    Mycobacterium tuberculosis complex (MTBC) refers to a group of mycobacteria encompassing nine members of closely related species that causes tuberculosis in animals and humans. Among the nine members, Mycobacterium tuberculosis (M. tuberculosis) remains the main causative agent for human tuberculosis that results in high mortality and morbidity globally. In general, MTBC species are low in diversity but exhibit distinctive biological differences and phenotypes among different MTBC lineages. MTBC species are likely to have evolved from a common ancestor through insertions/deletions processes resulting in species speciation with different degrees of pathogenicity. The pathogenesis of human tuberculosis is complex and remains poorly understood. It involves multi-interactions or evolutionary co-options between host factors and bacterial determinants for survival of the MTBC. Granuloma formation as a protection or survival mechanism in hosts by MTBC remains controversial. Additionally, MTBC species are capable of modulating host immune response and have adopted several mechanisms to evade from host immune attack in order to survive in humans. On the other hand, current diagnostic tools for human tuberculosis are inadequate and have several shortcomings. Numerous studies have suggested the potential of host biomarkers in early diagnosis of tuberculosis, in disease differentiation and in treatment monitoring. "Multi-omics" approaches provide holistic views to dissect the association of MTBC species with humans and offer great advantages in host biomarkers discovery. Thus, in this review, we seek to understand how the genetic variations in MTBC lead to species speciation with different pathogenicity. Furthermore, we also discuss how the host and bacterial players contribute to the pathogenesis of human tuberculosis. Lastly, we provide an overview of the journey of "omics" approaches in host biomarkers discovery in human tuberculosis and provide some interesting insights on the challenges and directions of "omics" approaches in host biomarkers innovation and clinical implementation.
    Matched MeSH terms: Tuberculosis/immunology*
  10. Interactions of domain antibody (dAbκ11) with Mycobacterium tuberculosis Ac2SGL in complex with CD1b
    Law CT, Camacho F, Garcia-Alles LF, Gilleron M, Sarmiento ME, Norazmi MN, et al.
    Tuberculosis (Edinb), 2019 01;114:9-16.
    PMID: 30711162 DOI: 10.1016/j.tube.2018.11.002
    Tuberculosis (TB) is the main cause of mortality among all infectious diseases. The presentation of lipids by CD1b molecules and the interactions of the CD1b-lipid complexes with the immune receptors are important for the understanding of the immune response to Mycobacterium tuberculosis (Mtb), and to develop TB control methods. A specific domain antibody (dAbk11) recognizing the complex of CD1b with Mtb sulphoglycolipid (Ac2SGL) had been previously developed. In order to study the interactions of dAbk11 with Ac2SGL:CD1b, the conformation of Ac2SGL within CD1b was first modelled. The orientation of dAbκ11 with Ac2SGL:CD1b was then predicted by a docking experiment and the complex was sampled using molecular dynamics simulation. Data showed that dAbκ11 Tyr32 OH plays a decisive role in interacting with Ac2SGL alkyl tail HO17. The binding free energy calculation showed that Ac2SGL establish strong hydrophobic interactions with dAbκ11. The model also predicted a higher affinity for the natural sulfoglycolipid (Ac2SGL) than the synthetic analogue (SGL12), which was supported by the ELISA data. These results shed light on the likely mechanism of interactions between Ac2SGL:CD1b and dAbκ11, thus making possible to envision the strategies for dAbκ11 optimization for possible future applications.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology; Tuberculosis/immunology*
  11. Fulltext Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
    Tan HY, Yong YK, Shankar EM, Paukovics G, Ellegård R, Larsson M, et al.
    J Immunol, 2016 05 15;196(10):4052-63.
    PMID: 27076678 DOI: 10.4049/jimmunol.1502203
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
    Matched MeSH terms: Tuberculosis/immunology*
  12. Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome
    Tan HY, Yong YK, Andrade BB, Shankar EM, Ponnampalavanar S, Omar SF, et al.
    AIDS, 2015 Feb 20;29(4):421-31.
    PMID: 25565499 DOI: 10.1097/QAD.0000000000000557
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS.
    Matched MeSH terms: Tuberculosis/immunology*
  13. Serum antigen 85 levels in adjunct testing for active mycobacterial infections in orangutans
    Kilbourn AM, Godfrey HP, Cook RA, Calle PP, Bosi EJ, Bentley-Hibbert SI, et al.
    J. Wildl. Dis., 2001 Jan;37(1):65-71.
    PMID: 11272506
    Diagnosis of active mycobacterial disease in orangutans (Pongo pygmaeus) has been impeded by high levels of non-specific intradermal skin test reactivity to mycobacterial antigens. This may be due in part to cross reactivity between antigens, tuberculin concentrations used or other species-specific factors. Antigen 85 (Ag85) complex proteins are major secretory products of actively growing mycobacteria, and measurement of serum Ag85 could provide a method for determining active mycobacterial infections that was not dependent on host immunity. Serum Ag85 was measured by dot-immunobinding assay using monoclonal anti-Ag85, purified Ag85 standard and enhanced chemiluminescence technology in coded serum samples from 14 captive orangutans from a zoo in Colorado, 15 semi-captive orangutans in Malaysia, and 19 free-ranging wild orangutans in Malaysia. Orangutans from Colorado (USA) were culture negative for Mycobacterium tuberculosis and M. avium, although all had laboratory suspicion or evidence of mycobacterial infection; median serum Ag85 was 10 microU/ml (range, <0.25-630 microU/ml). Of the semi-captive orangutans, six were skin test reactive and two were culture positive for M. avium on necropsy. Median serum Ag85 for this group was 1,880 microU/ml (0.75-7,000 microU/ml), significantly higher than that of Colorado zoo or free-ranging Malaysian orangutans. Median serum Ag85 in the latter group was 125 microU/ml (range, 0.75-2,500 microU/ml). These data suggest that suggest that additional studies using more specific reagents and more samples from animals of known status are appropriate.
    Matched MeSH terms: Tuberculosis/immunology
  14. Fulltext Tuberculosis: a resurgent disease in immunosuppressed patients
    Nissapatorn V, Kuppusamy I, Josephine FP, Jamaiah I, Rohela M, Khairul Anuar A
    Southeast Asian J. Trop. Med. Public Health, 2006;37 Suppl 3:153-60.
    PMID: 17547073
    A total of 136 patients, 67 HIV, 69 diabetes mellitus (DM) with or without (+/-) end-stage renal disease (ESRD), were registered for tuberculosis treatment at the National Tuberculosis Center (NTBC) from May to December, 2003. Ages ranged from 21-78 years (median 57.7 years) in TB/DM patients, and 21-62 (mean 37.6 +/- 8.3 years) in TB/HIV patients. TB was significantly found in younger and single HIV patients, but in older and married DM patients (p<0.05). Male patients in both groups were strongly associated with TB, while females more commonly had TB with DM (p<0.05). The majority of these patients were Malays, unemployed, and resided in Kuala Lumpur territory; however, no statistically significant difference was found between the 2 groups. Smoking, IVDUs and hepatitis C virus (HCV) infection were more significantly found in TB/HIV patients and further analysis showed that pulmonary TB was strongly associated with HCV infection in these patients (p<0.05). Pulmonary TB (62; 89.9%) was the most common type found in both groups and was a markedly more common disease location in TB/DM patients, while extrapulmonary TB (21; 31.3%) and miliary TB (14; 21%) were significantly higher in TB/HIV patients. Cough with or without sputum, fever and loss of appetite and/or weight were common clinical presentations in both groups. Nevertheless, fever (54; 80.6%) and lymphadenopathy (17; 25.4%) were significantly related to TB/HIV patients (p<0.05). Interestingly, the presence of BCG vaccination and positive tuberculin skin test were stronger in TB/HIV (27; 40.3%) and TB/DM (20; 29%) patients, respectively (p<0.05). Overall, regular 6-, 9- and 12-months' anti-tubercular therapy (ATT) were routine practice, and EHRZ+B6 was the most common regimen used. The highest percentage of patients with treatment success were in both groups with 6 months' ATT; however, a significantly higher percentage was found in TB/DM (24; 34.8%) than TB/HIV (13; 19.4%) (p<0.05). A success rate of 15 (21.7%) was noted for TB/DM patients with 9 months' ATT, which was similar to both groups with the 12-month regimen. A higher percentage failure rate (lost to follow-up) was seen in TB/HIV (19; 28.4%) patients. Nine patients were reported to have anti-tubercular-drug side-effects, such as drug-induced hepatitis, blurred vision, and skin rash. No cases of drug resistance or death were notified among these patients.
    Matched MeSH terms: Tuberculosis/immunology*
  15. Fulltext Tuberculosis disease diagnosis using artificial immune recognition system
    Shamshirband S, Hessam S, Javidnia H, Amiribesheli M, Vahdat S, Petković D, et al.
    Int J Med Sci, 2014;11(5):508-14.
    PMID: 24688316 DOI: 10.7150/ijms.8249
    There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods.
    Matched MeSH terms: Tuberculosis/immunology
  16. Genomic plasticity between human and mycobacterial DNA: A review
    Danjuma L, Ling MP, Hamat RA, Higuchi A, Alarfaj AA, Marlina, et al.
    Tuberculosis (Edinb), 2017 12;107:38-47.
    PMID: 29050770 DOI: 10.1016/j.tube.2017.03.006
    Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. After the cell division, the incorporated gene is reproduced normally and distributed proportionately between the two progeny. This inherent adoption of long-term persistence and incorporating the bacterial genetic material into that of the host tissue remains and is considered imperative for microbial advancement and chemotherapeutic resistance; moreover, new evidence indicates that the bacteria might pass on genetic material to the host DNA sequence. Several studies focused on the survival mechanism of M. tuberculosis in the host immune system with the aim of helping the efforts to discover new drugs and vaccines against tuberculosis. This review explored the mechanisms through which this bacterium affects the expression of human genes. The first part of the review summarizes the current knowledge about the interactions between microbes and host microenvironment, with special reference to the M. tuberculosis neglected persistence in immune cells and stem cells. Then, we focused on how bacteria can affect human genes and their expression. Furthermore, we analyzed the literature base on the process of cell death during tuberculosis infection, giving particular emphasis to gene methylation as an inherited process in the neutralization of possibly injurious gene components in the genome. The final section discusses recent advances related to the M. tuberculosis interaction with host epigenetic circuitry.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology; Latent Tuberculosis/immunology
  17. Does the Development of Vaccines Advance Solutions for Tuberculosis?
    AlMatar M, Makky EA, AlMandeal H, Eker E, Kayar B, Var I, et al.
    Curr Mol Pharmacol, 2019;12(2):83-104.
    PMID: 30474542 DOI: 10.2174/1874467212666181126151948
    BACKGROUND: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity. Based on these reasons, more efforts are channeled towards the development of new TB vaccines. During the development of TB vaccines, a major challenge has always been the lack of diversity in both the antigens contained in TB vaccines and the immune responses of the TB sufferers. Current efforts are channeled on widening both the range of antigens selection and the range of immune response elicited by the vaccines. The past two decades witnessed a significant progress in the development of TB vaccines; some of the discovered TB vaccines have recently even completed the third phase (phase III) of a clinical trial.

    OBJECTIVE: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.

    Matched MeSH terms: Mycobacterium tuberculosis/immunology; Tuberculosis/immunology
  18. Fulltext Comparative study of IgA VH 3 gene usage in healthy TST(-) and TST(+) population exposed to tuberculosis: deep sequencing analysis
    Chin ST, Ignatius J, Suraiya S, Tye GJ, Sarmiento ME, Acosta A, et al.
    Immunology, 2015 Feb;144(2):302-11.
    PMID: 25158076 DOI: 10.1111/imm.12372
    The acquired immune response against tuberculosis is commonly associated with T-cell responses with little known about the role of B cells or antibodies. There have been suggestions that B cells and humoral immunity can modulate the immune response to Mycobacterium tuberculosis. However, the mechanisms involving B-cell responses in M. tuberculosis are not fully understood, in particular the antibody gene preferences. We hypothesized that a preferential use of V genes can be seen associated with resistance to infection mainly in the IgA isotype, which is of prominent importance for infection by pathogens via the mucosal route. We studied healthy individuals with long-term exposure to tuberculosis, infected (TST(+) ) and uninfected TST(-) ) with M. tuberculosis. From a total of 22 V genes analysed, the TST(-) population preferred the VH 3-23 and Vκ1 genes. The VH 3-23 genes were subsequently subjected to 454 amplicon sequencing. The TST(-) population showed a higher frequency of the D3-10 segment compared with the D3-22 segment for the TST(+) population. The J segment usage pattern was similar for both populations with J4 segment being used the most. A preferential pairing of J4 segments to D3-3 was seen for the TST(-) population. The antibodyome difference between both populations suggests a preference for antibodies with VH 3-23, D3-3, JH 4 gene usage by the TST(-) population that could be associated with resistance to infection with M. tuberculosis.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology
  19. Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections
    Hamidon NH, Suraiya S, Sarmiento ME, Acosta A, Norazmi MN, Lim TS
    Appl Biochem Biotechnol, 2018 Mar;184(3):852-868.
    PMID: 28884285 DOI: 10.1007/s12010-017-2582-5
    B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 109 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.
    Matched MeSH terms: Mycobacterium tuberculosis/immunology*; Tuberculosis/immunology*
  20. Fulltext Sandwich Electrochemical Immunosensor for Early Detection of Tuberculosis Based on Graphene/Polyaniline-Modified Screen-Printed Gold Electrode
    Mohd Azmi UZ, Yusof NA, Kusnin N, Abdullah J, Suraiya S, Ong PS, et al.
    Sensors (Basel), 2018 Nov 14;18(11).
    PMID: 30441776 DOI: 10.3390/s18113926
    A rapid and sensitive sandwich electrochemical immunosensor was developed based on the fabrication of the graphene/polyaniline (GP/PANI) nanocomposite onto screen-printed gold electrode (SPGE) for detection of tuberculosis biomarker 10-kDa culture filtrate protein (CFP10). The prepared GP/PANI nanocomposite was characterized using Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). The chemical bonding and morphology of GP/PANI-modified SPGE were studied by Raman spectroscopy and FESEM coupled with energy dispersive X-ray spectroscopy, respectively. From both studies, it clearly showed that GP/PANI was successfully coated onto SPGE through drop cast technique. Cyclic voltammetry was used to study the electrochemical properties of the modified electrode. The effective surface area for GP/PANI-modified SPGE was enhanced about five times compared with bare SPGE. Differential pulse voltammetry was used to detect the CFP10 antigen. The GP/PANI-modified SPGE that was fortified with sandwich type immunosensor exhibited a wide linear range (20⁻100 ng/mL) with a low detection limit of 15 ng/mL. This proposed electrochemical immunosensor is sensitive, low sample volume, rapid and disposable, which is suitable for tuberculosis detection in real samples.
    Matched MeSH terms: Tuberculosis/immunology
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