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https://www.readbyqxmd.com/read/28429162/involvement-of-methylated-hbha-expressed-from-mycobacterium-smegmatis-in-an-ifn-%C3%AE-release-assay-to-aid-discrimination-between-latent-infection-and-active-tuberculosis-in-bcg-vaccinated-populations
#1
H-L Wen, C-L Li, G Li, Y-H Lu, H-C Li, T Li, H-M Zhao, K Wu, D B Lowrie, J-X Lv, S-H Lu, X-Y Fan
IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming...
April 20, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#2
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#3
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28425207/bcg-vaccination-induced-suppurative-lymphadenitis-four-signs-to-pay-attention-to
#4
Sang Oon Baek, Hyo Sun Ko, Hyun Ho Han
Suppurative lymphadenitis is one of the severe complication after BCG vaccination, but its diagnostic criteria and treatment guidelines have not yet been established. In this article, we describe a case of suppurative lymphadenitis caused by BCG vaccination and propose diagnostic criteria and treatment guidelines of the disease. The lymphadenitis was presented as skin involving mass and was completely extirpated. Pathological evaluation revealed a necrotising lymphadenitis, consistent with the diagnosis of BCG lymphadenitis...
April 19, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28424703/immune-responses-to-bacillus-calmette-gu%C3%A3-rin-vaccination-why-do-they-fail-to-protect-against-mycobacterium-tuberculosis
#5
REVIEW
Juan I Moliva, Joanne Turner, Jordi B Torrelles
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the current leading cause of death due to a single infectious organism. Although curable, the broad emergence of multi-, extensive-, extreme-, and total-drug resistant strains of M.tb has hindered eradication efforts of this pathogen. Furthermore, computational models predict a quarter of the world's population is infected with M.tb in a latent state, effectively serving as the largest reservoir for any human pathogen with the ability to cause significant morbidity and mortality...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424682/interactions-between-type-1-interferons-and-the-th17-response-in-tuberculosis-lessons-learned-from-autoimmune-diseases
#6
REVIEW
Bas C Mourik, Erik Lubberts, Jurriaan E M de Steenwinkel, Tom H M Ottenhoff, Pieter J M Leenen
The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28414012/reasons-for-optimism-in-the-search-for-new-vaccines-for-tuberculosis
#7
T G Evans
In the development of vaccines for tuberculosis (TB), the combination of the will, funding, scientific rigor, new tools, refined animal models and improved clinical trial designs are all converging at an opportune moment. The lack of optimism that has surrounded the likelihood for finding novel TB vaccines has resulted from a lack of correlates of vaccine-induced protection, a lack of tool candidate vaccines to probe the immunologic space, which may be needed, and the negative result of one recent trial. A vaccine for TB that can be delivered at a reasonable cost to the marketplace will have greater impact on the incidence of new cases of TB than any intervention in world history...
April 17, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28411454/synthesis-and-immunogenicity-of-pg-tb1-monovalent-glycoconjugate
#8
Xin Meng, Chuanming Ji, Chao Su, Di Shen, Yaxin Li, Peijie Dong, Ding Yuan, Mengya Yang, Song Bai, Demei Meng, Zhenchuan Fan, Yang Yang, Peng Yu, Tao Zhu
A PG-tb1 hapten from the West Beijing strains of Mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to CRM197 in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent T-dependent conjugate vaccine. The intermediate monoester can be easily purified and the degree of incorporation can be monitored by MALDI-TOF mass spectrometry. After administered systemically in mice without any adjuvant, the conjugate induced high antigen-specific IgG levels in serum...
March 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28404472/the-prevalence-of-latent-tuberculosis-infection-in-rural-jiangsu-china
#9
Y Liu, S Huang, H Jiang, J Xiong, Y Wang, M Ou, J Cai, C Yang, Z Wang, S Ge, N Xia
OBJECTIVES: Diagnosis and interventional treatment of latent tuberculosis (TB) infection (LTBI) are important components in tuberculosis control. But systematic studies regarding the epidemic of LTBI are still rare in China. The objective of this study was to assess the prevalence and risk factors associated with LTBI based on the results of a domestic TB-specific gamma interferon (IFN-γ) release assay (TB-IGRA) in rural Jiangsu, China. STUDY DESIGN: Cross-sectional study of subjects registered in eight villages in Jiangsu, China...
February 4, 2017: Public Health
https://www.readbyqxmd.com/read/28401156/computational-identification-and-characterization-of-a-promiscuous-t-cell-epitope-on-the-extracellular-protein-85b-of-mycobacterium-spp-for-peptide-based-subunit-vaccine-design
#10
Md Saddam Hossain, Abul Kalam Azad, Parveen Afroz Chowdhury, Mamoru Wakayama
Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28399967/type-1-polarised-dendritic-cells-are-a-potent-immunogen-against-mycobacterium-tuberculosis
#11
Y Satake, Y Nakamura, M Kono, H Hozumi, T Nagata, K Tsujimura, N Enomoto, T Fujisawa, N Inui, T Fujiyama, Y Tokura, T Matsui, K Yokomura, M Shirai, H Hayakawa, T Suda
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6)...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28387329/introducing-the-esat-6-free-igra-a-companion-diagnostic-for-tb-vaccines-based-on-esat-6
#12
Morten Ruhwald, Lena de Thurah, Davis Kuchaka, Mostafa Rafaat Zaher, Ahmed M Salman, Abdel-Rahman Abdel-Ghaffar, Faten Aly Shoukry, Sascha Wilk Michelsen, Bolette Soborg, Thomas Blauenfeldt, Stellah Mpagama, Søren T Hoff, Else Marie Agger, Ida Rosenkrands, Claus Aagard, Gibson Kibiki, Nabila El-Sheikh, Peter Andersen
There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374535/association-of-esat-6-cfp-10-induced-ifn-%C3%AE-tnf-%C3%AE-and-il-10-with-clinical-tuberculosis-evidence-from-cohorts-of-pulmonary-tuberculosis-patients-household-contacts-and-community-controls-in-an-endemic-setting
#13
F Abebe, M Belay, M Legesse, A Mihret, K S Franklin
Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity (IFN-γ production), while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT-6/CFP-10 during natural Mtb infections in humans has not been established...
April 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28367799/risk-of-tuberculosis-among-air-passengers-estimated-by-interferon-gamma-release-assay-survey-of-contact-investigations-japan-2012-to-2015
#14
Masaki Ota, Seiya Kato
Although the World Health Organization recommends contact investigations around air travel-associated sputum smear-positive tuberculosis (TB) patients, evidence suggests that the information thus obtained may have overestimated the risk of TB infection because it involved some contacts born in countries with high TB burden who were likely to have been infected with TB in the past, or because tuberculin skin tests were used, which are less specific than the interferon gamma release assay (IGRA) particularly in areas where Bacillus Calmette-Guérin (BCG) vaccination coverage is high...
March 23, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28359736/hla-a-b-drb1-dqa1-dqb1-alleles-and-haplotype-frequencies-in-dene-and-cree-cohorts-in-manitoba-canada
#15
Linda A Larcombe, Leigh Anne Shafer, Peter W Nickerson, Andrew M Lodge, Jodie S Brown, Leisel C Milligan, Denise Pochinco, Lynnette Beaudin, Brian Arundel, Jacqueline Wong, Joe Dantouze, Lizette Denechezhe, Pamela H Orr
BACKGROUND: First Nations in the Canadian province of Manitoba have disproportionately high rates of epidemic and endemic TB. Gene polymorphisms that modulate HLA Class I and II antigens are among the risk markers for TB, along with other biologic, and social determinants of health. HLA-A, B, DRB1, DQA1, DQB1 were typed in two Manitoba First Nation indigenous groups to identify and compare the frequency of gene polymorphisms that may influence susceptibility or resistance to TB. METHODS: Participants who self-identified as either Dene or Cree enrolled into the study from two First Nation communities in Manitoba, Canada...
March 27, 2017: Human Immunology
https://www.readbyqxmd.com/read/28359325/early-versus-late-bcg-vaccination-in-hiv-1-exposed-infants-in-uganda-study-protocol-for-a-randomized-controlled-trial
#16
Victoria Nankabirwa, James K Tumwine, Olive Namugga, Thorkild Tylleskär, Grace Ndeezi, Bjarne Robberstad, Mihai G Netea, Halvor Sommerfelt
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB)...
March 31, 2017: Trials
https://www.readbyqxmd.com/read/28348981/ppe38-protein-of-mycobacterium-tuberculosis-inhibits-macrophage-mhc-class-i-expression-and-dampens-cd8-t-cell-responses
#17
Lu Meng, Jingfeng Tong, Hui Wang, Chengwu Tao, Qinglan Wang, Chen Niu, Xiaoming Zhang, Qian Gao
Suppression of CD8(+) T cell activation is a critical mechanism used by Mycobacterium tuberculosis (MTB) to escape protective host immune responses. PPE38 belongs to the unique PPE family of MTB and in our previous study, PPE38 protein was speculated to participate in manipulating macrophage MHC class I pathway. To test this hypothesis, the function of mycobacterial PPE38 protein was assessed here using macrophage and mouse infection models. Decreased amount of MHC class I was observed on the surface of macrophages infected with PPE38-expressing mycobacteria...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28348866/integrated-computational-prediction-and-experimental-validation-identifies-promiscuous-t-cell-epitopes-in-the-proteome-of-mycobacterium-bovis
#18
Damien Farrell, Gareth Jones, Christopher Pirson, Kerri Malone, Kevin Rue-Albrecht, Anthony J Chubb, Martin Vordermeier, Stephen V Gordon
The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4(+) T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M...
August 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28348055/the-enigmatic-pe-ppe-multi-gene-family-of-mycobacteria-and-tb-vaccination
#19
Michael J Brennan
The genome of Mycobacterium tuberculosis (Mtb), the bacteria responsible for the disease tuberculosis, contains an unusual family of abundant antigens (PE/PPEs) . To date certain members of this multigene family occur only in mycobacteria that cause disease. It is possible that the numerous proteins encoded by these mycobacterial genes dictate the immune-pathogenesis of this bacterial pathogen. There is also evidence that some of these antigens are present at the cell surface and that they affect the pathology and immunology of the organism in many ways...
March 27, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28342639/sendai-virus-mucosal-vaccination-establishes-lung-resident-memory-cd8%C3%A2-t-cell-immunity-and-boosts-bcg-primed-protection-against-tb-in-mice
#20
Zhidong Hu, Ka-Wing Wong, Hui-Min Zhao, Han-Li Wen, Ping Ji, Hui Ma, Kang Wu, Shui-Hua Lu, Feng Li, Zhong-Ming Li, Tsugumine Shu, Jian-Qing Xu, Douglas B Lowrie, Xiao-Yong Fan
Accumulating evidence has shown the protective role of CD8(+) T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8(+) T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice...
March 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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