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https://www.readbyqxmd.com/read/29034213/a-promising-listeria-vectored-vaccine-induces-th1-type-immune-responses-and-confers-protection-against-tuberculosis
#1
Yuelan Yin, Kai Lian, Dan Zhao, Chengwu Tao, Xiang Chen, Weijun Tan, Xiaobo Wang, Zhengzhong Xu, Maozhi Hu, Yan Rao, Xiaohui Zhou, Zhiming Pan, Xiaoming Zhang, Xin'an Jiao
Deaths associated with tuberculosis (TB) is rising and accounted for 1.4 million deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines represent an important medical intervention, but the current Bacilli Calmette-Guerin (BCG) vaccine is not ideal for the protection of teenagers and adults. Therefore, a safe and effective vaccine is urgently needed. In this study, we designed a novel vaccine using an attenuated Listeria monocytogenes strain carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29028973/safety-and-immunogenicity-of-newborn-mva85a-vaccination-and-selective-delayed-bacille-calmette-guerin-bcg-for-infants-of-hiv-infected-mothers-a-phase-2-randomized-controlled-trial
#2
Elisa Nemes, Anneke C Hesseling, Michele Tameris, Katya Mauff, Katrina Downing, Humphrey Mulenga, Penelope Rose, Marieke van der Zalm, Sharon Mbaba, Danelle Van As, Willem A Hanekom, Gerhard Walzl, Thomas J Scriba, Helen McShane, Mark Hatherill
Background: Vaccination of HIV-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis (TB) vaccination strategy that protects against TB early in life; and avoids the potential risk of BCG disease until after HIV infection has been excluded. Methods: This double-blind randomized controlled trial compared newborn MVA85A prime vaccination (1 x10 8 PFU) vs. Candin® control, followed by selective deferred BCG vaccination at 8 weeks of age for HIV-uninfected infants, and 12 months follow-up for safety and immunogenicity...
September 26, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29025083/the-duration-of-protection-of-school-aged-bcg-vaccination-in-england-a-population-based-case-control-study
#3
Punam Mangtani, Patrick Nguipdop-Djomo, Ruth H Keogh, Jonathan A C Sterne, Ibrahim Abubakar, Peter G Smith, Paul E M Fine, Emilia Vynnycky, John M Watson, David Elliman, Marc Lipman, Laura C Rodrigues
Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. Methods: We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls...
August 31, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29017616/quantitative-interferon-gamma-responses-predict-future-disease-progression-in-badgers-naturally-infected-with-mycobacterium-bovis
#4
S N Buzdugan, M A Chambers, R J Delahay, J A Drewe
The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis: TB) continues to present huge challenges to the British cattle industry. A clearer understanding of the magnitude and duration of immune response to M. bovis infection in the European badger (Meles meles) - a wildlife maintenance host - may assist with the future development of diagnostic tests, and vaccination and disease management strategies. Here, we analyse 5280 diagnostic test results from 550 live wild badgers from a naturally-infected population to investigate whether one diagnostic test (a gamma interferon release [IFNγ] assay, n = 550 tests) could be used to predict future positive results on two other tests for the same disease (a serological test [n = 2342 tests] and mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely bacterial excretion or disease progression...
October 11, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28990539/new-drugs-and-vaccines-for-tuberculosis
#5
S Beg, Praveen Gaur, Shikha Mishra
Tuberculosis (TB) is an infectious disease that resulted in estimated 9.6 million new cases in 2014 and 1.5 million deaths. The available drug regimen for TB is time consuming which more often leads to the patient non compliance which then results in occurrence of drug resistant TB (Multi-drug and extremely drug resistant TB) in several portions of the world. The dangerous combinations of TB and HIV is taking its toll on human health. The foremost factor is non- profit associated with the development of anti TB drugs...
October 6, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#6
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28974949/the-recombinant-bacille-calmette-gu%C3%A3-rin-vaccine-vpm1002-ready-for-clinical-efficacy-testing
#7
REVIEW
Natalie E Nieuwenhuizen, Prasad S Kulkarni, Umesh Shaligram, Mark F Cotton, Cyrill A Rentsch, Bernd Eisele, Leander Grode, Stefan H E Kaufmann
The only licensed vaccine against tuberculosis (TB), bacille Calmette-Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28974092/poly-i-c-encapsulating-nanoparticles-enhance-innate-immune-responses-to-the-tuberculosis-vaccine-bacille-calmette-gu%C3%A3-rin-bcg-via-synergistic-activation-of-innate-immune-receptors
#8
Martin T Speth, Urska Repnik, Elisabeth Müller, Julia Spanier, Ulrich Kalinke, Alexandre Corthay, Gareth Griffiths
The attenuated live vaccine strain Bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3) to enhance the immunogenicity of BCG in mouse bone marrow-derived macrophages (BMDM) in vitro...
October 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28967465/conjugation-of-the-crm197-inulin-conjugate-significantly-increases-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#9
Shun Hu, Weili Yu, Chunyang Hu, Dong Wei, Lijuan Shen, Tao Hu, Youjin Yi
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen that causes tuberculosis (TB). Effective vaccination is urgently needed to deal with the serious threat from TB. Mtb-secreted protein antigens are important virulence determinants of Mtb with poor immunogenicity. Adjuvants and antigen delivery systems are thus highly desired to improve the immunogenicity of protein antigens. Inulin is a biocompatible polysaccharide (PS) adjuvant that can stimulate a strong cellular and humoral immunity. Bacterial capsular PS and haptens have been conjugated with cross-reacting material 197 (CRM197) to improve their immunogenicity...
September 19, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28955344/what-have-we-learnt-about-bcg-vaccination-in-the-last-20%C3%A2-years
#10
REVIEW
Hazel M Dockrell, Steven G Smith
A number of new tuberculosis (TB) vaccines have been or are entering clinical trials, which include genetically modified mycobacteria, mycobacterial antigens delivered by viral vectors, or mycobacterial antigens in adjuvant. Some of these vaccines aim to replace the existing BCG vaccine but others will be given as a boosting vaccine following BCG vaccination given soon after birth. It is clear that the existing BCG vaccines provide incomplete and variable protection against pulmonary TB. This review will discuss what we have learnt over the last 20 years about how the BCG vaccine induces specific and non-specific immunity, what factors influence the immune responses induced by BCG, and progress toward identifying correlates of immunity against TB from BCG vaccination studies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28955338/cellular-architecture-of-spinal-granulomas-and-the-immunological-response-in-tuberculosis-patients-coinfected-with-hiv
#11
Debapriya Bhattacharya, Siva Danaviah, Daniel M Muema, Ngomu Akeem Akilimali, Prashini Moodley, Thumbi Ndung'u, Gobardhan Das
Mycobacterium tuberculosis (M.tb) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28951586/anti-mycobacterial-activity-correlates-with-altered-dna-methylation-pattern-in-immune-cells-from-bcg-vaccinated-subjects
#12
Deepti Verma, Venkata Ramanarao Parasa, Johanna Raffetseder, Mihaela Martis, Ratnesh B Mehta, Mihai Netea, Maria Lerm
The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a sub-group of BCG-vaccinated individuals (identified as 'responders')...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28948453/the-efficacy-of-latent-tuberculosis-treatment-for-immunocompetent-uveitis-patients-with-a-positive-t-spot-tb-test-6-year-experience-in-a-tuberculosis-endemic-region
#13
Chung Yee Chung, Kenneth K W Li
PURPOSE: To assess the efficacy of latent tuberculosis (TB) treatment for immunocompetent uveitis patients with a positive T-SPOT.TB test. METHODS: This is a consecutive case series of all T-SPOT.TB positive latent TB patients with presumed tuberculous uveitis managed with anti-tuberculous therapy (ATT) from 1 January 2000 to 31 December 2015. Patients with active TB or other known causes of uveitis, immunocompromised states and those followed up < 12 months were excluded...
September 25, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28943726/designing-epitope-ensemble-vaccines-against-tb-by-selection-prioritizing-antigens-using-predicted-immunogenicity
#14
Jaymisha Mistry, Darren R Flower
Tuberculosis (TB) is a global health burden, and a major cause of mortality and morbidity in West Africa. Here, we select key conserved pathogen epitopes of proven immunogenicity to form a potential TB epitope ensemble vaccine. We compared two vaccine formulations: one comprising class I epitopes from the 13 most prevalent class I epitope-bearing antigens and class II epitopes deriving from the 20 most prevalent class II epitope-bearing antigens and another consisting of epitopes derived solely from 5 antigens identified as the most immunogenic by VaxiJen...
2017: Bioinformation
https://www.readbyqxmd.com/read/28941991/conservation-in-gene-encoding-mycobacterium-tuberculosis-antigen-rv2660-and-a-high-predicted-population-coverage-of-h56-multistage-vaccine-in-south-africa
#15
Angy P Perez-Martinez, Edison Ong, Lixin Zhang, Carl F Marrs, Yongqun He, Zhenhua Yang
H56/AERAS-456+IC31 (H56), composed of two early secretion proteins, Ag85B and ESAT-6, and a latency associated protein, Rv2660, and the IC31 Intercell adjuvant, is a new fusion subunit vaccine candidate designed to induce immunity against both new infection and reactivation of latent tuberculosis infection. Efficacy of subunit vaccines may be affected by the diversity of vaccine antigens among clinical strains and the extent of recognition by the diverse HLA molecules in the recipient population. Although a previous study showed the conservative nature of Ag85B- and ESAT-6-encoding genes, genetic diversity of Rv2660c that encodes RV2660 is largely unknown...
September 21, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28941042/nanomaterials-in-the-prevention-diagnosis-and-treatment-of-mycobacterium-tuberculosis-infections
#16
REVIEW
Kaijin Xu, Zhen Chang Liang, Xin Ding, Haiyang Hu, Shaoqiong Liu, Martin Nurmik, Sheng Bi, Feishu Hu, Zhongkang Ji, Jingjing Ren, Shigui Yang, Yi Yan Yang, Lanjuan Li
Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment...
September 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28937879/advax4-delta-inulin-combination-adjuvant-together-with-ecmx-a-fusion-construct-of-three-protective-mtb-antigens-induces-a-potent-th1-immune-response-and-protects-mice-against-mycobacterium-tuberculosis-infection
#17
Bruno de Paula Oliveira Santos, Monalisa Martins Trentini, Renato Beilner Machado, Mara Rúbia Nunes Celes, André Kipnis, Nikolai Petrovsky, Ana Paula Junqueira-Kipnis
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMXformulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. When BALB/c mice were immunized three times intramuscularly with these vaccine formulationsInjection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b(+)) in the draining lymph nodes consistent with a chemotactic adjuvant effect...
September 22, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28935575/non-pathological-infection-of-macaques-by-an-attenuated-mycobacterial-vaccine-is-not-reactivated-in-the-setting-of-hiv-coinfection
#18
Taylor Wayne Foreman, Ashley Victoria Veatch, Denae Nadine LoBato, Peter John Didier, Lara Angela Doyle-Meyers, Kasi Elizabeth Russell-Lodrigue, Andrew Alan Lackner, Konstantin Gus Kousoulas, Shabaana Abdul Khader, Deepak Kaushal, Smriti Mehra
Failure to replace BCG with efficacious anti-TB vaccines have prompted out-of-the-box thinking, including pulmonary vaccination in order to elicit local immunity. MtbΔsigH, a stress-response attenuated strain, protected against lethal TB when used to vaccinate macaques via inhalation. While live mycobacterial vaccines show promising efficacy, HIV co-infection and the resulting immunodeficiency prompts safety concerns about their use. We assessed the persistence and safety of MtbΔsigH, delivered directly to the lungs, in the setting of HIV coinfection...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28930287/exposure-to-human-alveolar-lining-fluid-enhances-mycobacterium-bovis-bcg-vaccine-efficacy-against-mycobacterium-tuberculosis-infection-in-a-cd8-t-cell-dependent-manner
#19
J I Moliva, A P Hossfeld, C H Canan, V Dwivedi, M D Wewers, G Beamer, J Turner, J B Torrelles
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28927311/successes-and-failures-in-human-tuberculosis-vaccine-development
#20
Roberto Zenteno-Cuevas
Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines...
September 19, 2017: Expert Opinion on Biological Therapy
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