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https://www.readbyqxmd.com/read/28531291/a-novel-virus-vectored-respiratory-mucosal-vaccine-enhances-anti-tuberculosis-immunity-in-a-humanized-model-system
#1
Yushi Yao, Rocky Lai, Sam Afkhami, Siamak Haddadi, Anna Zganiacz, Fatemeh Vahedi, Ali A Ashkar, Charu Kaushic, Mangalakumari Jeyanathan, Zhou Xing
Background: The translation of pre-clinically promising novel tuberculosis (TB) vaccines to ultimate human applications has met with the challenge of lacking markedly improved animal models for vaccine testing with an immune system of human equivalent in its genetic diversity and level of susceptibility to TB. Methods: We have developed a humanized mice (Hu-mice) TB model system to investigate the clinical relevance of a novel virus-vectored (VV) TB vaccine administered via respiratory mucosal (RM) or parenteral route...
May 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#2
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28525582/challenges-in-the-estimation-of-the-annual-risk-of-mycobacterium-tuberculosis-infection-in-children-aged-under-5-years
#3
P Y Khan, J R Glynn, T Mzembe, D Mulawa, R Chiumya, A C Crampin, K Kranzer, K L Fielding
Accurate estimates of Mycobacterium tuberculosis (M.tb) infection in young children provide a critical indicator of on-going community M.tb transmission. Cross reactions due to infection with environmental mycobacteria and/or Bacille Calmette-Guérin (BCG) vaccination compromise the estimates derived from population-level tuberculin skin test surveys using traditional cut-off methods. Newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalence of M.tb infection is low and environmental sensitisation is high...
May 19, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28522990/animal-models-for-tuberculosis-in-translational-and-precision-medicine
#4
REVIEW
Lingjun Zhan, Jun Tang, Mengmeng Sun, Chuan Qin
Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28515626/the-history-of-tuberculosis-from-the-first-historical-records-to-the-isolation-of-koch-s-bacillus
#5
REVIEW
I Barberis, N L Bragazzi, L Galluzzo, M Martini
Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium tuberculosis (MT) that has always been a permanent challenge over the course of human history, because of its severe social implications. It has been hypothesized that the genus Mycobacterium originated more than 150 million years ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of TB. The illness was known in England and France as "king's evil", and it was widely believed that persons affected could heal after a royal touch...
March 2017: Journal of Preventive Medicine and Hygiene
https://www.readbyqxmd.com/read/28510418/conjugation-reaction-with-8-arm-peg-markedly-improves-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#6
Xiaowei Sun, Weili Yu, Quanhai Pang, Tao Hu
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. CFP10 and TB10.4 are two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen...
May 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28507027/mycobacterium-tuberculosis-lipoprotein-mpt83-induces-apoptosis-of-infected-macrophages-by-activating-the-tlr2-p38-cox-2-signaling-pathway
#7
Lin Wang, Mianyong Zuo, Hao Chen, Siyu Liu, Xiangyang Wu, Zhenling Cui, Hua Yang, Haipeng Liu, Baoxue Ge
Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious global health threat. The attenuated Mycobacterium bovis bacillus Calmette-Guérin, as the only licensed vaccine, has limited protective efficacy against TB. The development of more effective antituberculosis vaccines is urgent and demands for further identification and understanding of M. tuberculosis Ags. MPT83 (Rv2873), a secreted mycobacterial lipoprotein, has been applied into subunit vaccine development and shown protective effects against M...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28479800/factors-determining-the-clinical-spectrum-course-and-response-to-treatment-and-complications-in-seronegative-patients-with-central-nervous-system-tuberculosis
#8
Sadanandavalli Retnaswami Chandra, Sikandar Advani, Ravi Kumar, Chandrajith Prasad, Anupama R Pai
INTRODUCTION: Tuberculous meningitis remains a major health issue in the community affecting young adults of both genders predominantly from rural background. In India, the disease continues to kill 2 people every 3 min or nearly 1000 daily, according to the Tuberculosis Control Society India. Tuberculosis (TB) of central nervous system (CNS) is the most devastating form of TB. As this disease is associated with very high prevalence in young adults and will ultimately contribute to great workforce loss, we decided to assess the factors deciding the disease and its course in our patients...
April 2017: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28476627/-the-impact-of-mycobacterium-tuberculosis-immune-evasion-on-protective-immunity-implications-for-tb-vaccine-design-meeting-report
#9
Cesar Boggiano, Katrin Eichelberg, Lakshmi Ramachandra, Jaqueline Shea, Lalita Ramakrishnan, Samuel Behar, Joel D Ernst, Steven A Porcelli, Markus Maeurer, Hardy Kornfeld
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28472067/the-effect-of-current-schistosoma-mansoni-infection-on-the-immunogenicity-of-a-candidate-tb-vaccine-mva85a-in-bcg-vaccinated-adolescents-an-open-label-trial
#10
Anne Wajja, Dennison Kizito, Beatrice Nassanga, Angela Nalwoga, Joyce Kabagenyi, Simon Kimuda, Ronald Galiwango, Gertrude Mutonyi, Samantha Vermaak, Iman Satti, Jaco Verweij, Edridah Tukahebwa, Stephen Cose, Jonathan Levin, Pontiano Kaleebu, Alison M Elliott, Helen McShane
INTRODUCTION: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. METHODS: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28463648/a-functional-tollip-variant-is-associated-with-bcg-specific-immune-responses-and-tuberculosis
#11
Javeed A Shah, Munyaradzi Musvosvi, Muki Shey, David J Horne, Richard D Wells, Glenna J Peterson, Jeffery S Cox, Michelle Daya, Eileen G Hoal, Lin Lin, Raphael Gottardo, Willem A Hanekom, Thomas J Scriba, Mark Hatherill, Thomas R Hawn
RATIONALE: The molecular mechanisms that regulate tuberculosis susceptibility and BCG-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of M. tuberculosis. TOLLIP is a ubiquitin-binding protein that regulates innate immune responses, including TLR signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood...
May 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28454649/variable-bcg-efficacy-in-rhesus-populations-pulmonary-bcg-provides-protection-where-standard-intra-dermal-vaccination-fails
#12
Frank A W Verreck, Elma Z Tchilian, Richard A W Vervenne, Claudia C Sombroek, Ivanela Kondova, Okke A Eissen, Vinod Sommandas, Nicole M van der Werff, Ernst Verschoor, Gerco Braskamp, Jaco Bakker, Jan A M Langermans, Peter J Heidt, Tom H M Ottenhoff, Klaas W van Kralingen, Alan W Thomas, Peter C L Beverley, Clemens H M Kocken
M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable protective efficacy in different human populations. In non-human primate studies using rhesus macaques, despite efforts to standardise the model, we have also observed variable efficacy of BCG upon subsequent experimental M. tuberculosis challenge. In the present head-to-head study, we establish that the protective efficacy of standard parenteral BCG immunisation varies among different rhesus cohorts. This provides different dynamic ranges for evaluation of investigational vaccines, opportunities for identifying possible correlates of protective immunity and for determining why parenteral BCG immunisation sometimes fails...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454648/the-siglec14-null-allele-is-associated-with-mycobacterium-tuberculosis-and-bcg-induced-clinical-and-immunologic-outcomes
#13
Andrew D Graustein, David J Horne, Jerry J Fong, Flavio Schwarz, Heather C Mefford, Glenna J Peterson, Richard D Wells, Munyaradzi Musvosvi, Muki Shey, Willem A Hanekom, Mark Hatherill, Thomas J Scriba, Nguyen Thuy Thuong Thuong, Nguyen Thi Hoang Mai, Maxine Caws, Nguyen Duc Bang, Sarah J Dunstan, Guy E Thwaites, Ajit Varki, Takashi Angata, Thomas R Hawn
Humans exposed to Mycobacterium tuberculosis (Mtb) have variable susceptibility to tuberculosis (TB) and its outcomes. Siglec-5 and Siglec-14 are members of the sialic-acid binding lectin family that regulate immune responses to pathogens through inhibitory (Siglec-5) and activating (Siglec-14) domains. The SIGLEC14 coding sequence is deleted in a high proportion of individuals, placing a SIGLEC5-like gene under the expression of the SIGLEC14 promoter (the SIGLEC14 null allele) and causing expression of a Siglec-5 like protein in monocytes and macrophages...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28453555/multi-subunit-bcg-booster-vaccine-gamtbvac-assessment-of-immunogenicity-and-protective-efficacy-in-murine-and-guinea-pig-tb-models
#14
A P Tkachuk, V A Gushchin, V D Potapov, A V Demidenko, V G Lunin, A L Gintsburg
New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models...
2017: PloS One
https://www.readbyqxmd.com/read/28447476/mtbvac-from-discovery-to-clinical-trials-in-tuberculosis-endemic-countries
#15
Dessislava Marinova, Jesus Gonzalo-Asensio, Nacho Aguilo, Carlos Martin
BCG remains the only vaccine against tuberculosis (TB) in use today and despite its impressive global coverage, the nature of BCG protection against the pulmonary forms of TB remains subject to ongoing debate. Because of the limitations of BCG, novel TB vaccine candidates have been developed and several have reached the clinical pipeline. One of these candidates is MTBVAC, the first and only TB vaccine in the clinical pipeline to date based on live-attenuated Mycobacterium tuberculosis that has successfully entered clinical evaluation, a historic milestone in human vaccinology...
June 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28446902/modulation-of-macrophage-responses-by-cmx-a-fusion-protein-composed-of-ag85c-mpt51-and-hspx-from-mycobacterium-tuberculosis
#16
Adeliane C da Costa, Danilo P de Resende, Bruno de P O Santos, Karina F Zoccal, Lúcia H Faccioli, André Kipnis, Ana P Junqueira-Kipnis
Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#17
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
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
#18
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
#19
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
#20
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
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