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https://www.readbyqxmd.com/read/28646952/drug-resistant-tuberculosis-primary-transmission-and-management
#1
Alexander C Outhred, Philip N Britton, Ben J Marais
The DOTS strategy assisted global tuberculosis (TB) control, but was unable to prevent the emergence and spread of drug-resistant strains. Genomic evidence confirms the transmission of drug-resistant Mycobacterium tuberculosis strains in many different settings, indicative of epidemic spread. These findings emphasise the need for enhanced infection control measures in health care and congregate settings. Young children in TB endemic areas are particularly vulnerable. Although advances in TB drug and vaccine development are urgently needed, improved access to currently available preventive therapy and treatment for drug resistant TB could reduce the disease burden and adverse outcomes experienced by children...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28646324/expression-purification-and-characterization-of-gmz2-10c-a-complex-disulphide-bonded-fusion-protein-vaccine-candidate-against-the-asexual-and-sexual-life-stages-of-the-malaria-causing-plasmodium-falciparum-parasite
#2
Ulrik H Mistarz, Susheel K Singh, Tam T T N Nguyen, Will Roeffen, Fen Yang, Casper Lissau, Søren M Madsen, Astrid Vrang, Régis W Tiendrebeogo, Ikhlaq H Kana, Robert W Sauerwein, Michael Theisen, Kasper D Rand
PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method...
June 23, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#3
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28633702/impact-of-isoniazid-preventive-therapy-on-the-evaluation-of-long-term-effectiveness-of-infant-mva85a-vaccination
#4
E W Bunyasi, A K K Luabeya, M Tameris, H Geldenhuys, H Mulenga, B S Landry, T J Scriba, B-M Schmidt, W A Hanekom, H Mahomed, H McShane, M Hatherill
SETTING: South Africa. OBJECTIVE: To evaluate the long-term effectiveness of infant modified vaccinia Ankara virus-expressing antigen 85A (MVA85A) vaccination against tuberculosis (TB). DESIGN: We analysed data from a double-blind randomised placebo-controlled Phase 2b MVA85A infant TB vaccine trial (2009-2012), with extended post-trial follow-up (2012-2014). Isoniazid preventive therapy (IPT) was provided by public health services according to national guidelines...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28625522/immunogenicity-and-therapeutic-effects-of-recombinant-ag85ab-fusion-protein-vaccines-in-mice-infected-with-mycobacterium-tuberculosis
#5
Yan Liang, Junxian Zhang, Yourong Yang, Xuejuan Bai, Qi Yu, Ning Li, Ying Hou, Yingchang Shi, Lan Wang, Xueqiong Wu
The immune function of tuberculosis (TB) patients is disordered. By using immune regulators to assist chemotherapy for TB the curative effect might be improved. In this study, a vaccine containing Mycobacterium tuberculosis (M. tuberculosis) recombinant Ag85AB fusion protein (rAg85AB) was constructed and evaluated. The mice were immunized intramuscularly three times at two-week intervals with Ag85AB fusion protein combined with Corynebacterium parvum adjuvant (rAg85AB+CP). In comparison to control mice that received either CP alone or saline, the mice that received rAg85AB+CP had significantly higher number of T cells secreting IFN-γ and higher levels of specific antibodies of IgG, IgG1 and IgG2a isotypes in sera...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28620588/immunogenicity-and-protective-efficacy-of-a-fusion-protein-tuberculosis-vaccine-combining-five-esx-family-proteins
#6
Zhi-Hao Xiang, Rui-Feng Sun, Chen Lin, Fu-Zeng Chen, Jun-Tao Mai, Yu-Xiao Liu, Zi-Yan Xu, Lu Zhang, Jun Liu
One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4(+) T cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28618268/antigen-availability-shapes-t-cell-differentiation-and-function-during-tuberculosis
#7
Albanus O Moguche, Munyaradzi Musvosvi, Adam Penn-Nicholson, Courtney R Plumlee, Helen Mearns, Hennie Geldenhuys, Erica Smit, Deborah Abrahams, Virginie Rozot, One Dintwe, Søren T Hoff, Ingrid Kromann, Morten Ruhwald, Peter Bang, Ryan P Larson, Shahin Shafiani, Shuyi Ma, David R Sherman, Alessandro Sette, Cecilia S Lindestam Arlehamn, Denise M McKinney, Holden Maecker, Willem A Hanekom, Mark Hatherill, Peter Andersen, Thomas J Scriba, Kevin B Urdahl
CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28617538/recent-advances-in-management-of-tuberculosis-in-infants
#8
Q Zhen, C-L Zhang, L Gong
The global tuberculosis (TB) incidence estimated by WHO is found to be 8.6 million people. Moreover, the highest TB burden worldwide is found in Asian and African countries. The disease is more prevalent in infants due to their immature immune systems. Despite this, the available diagnostic tools pose a challenge due to paucibacillary nature of the disease and difficulty in obtaining specimens. The present review article discusses the important and upcoming advancements in the management of above pathological state...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28615077/service-utilization-and-cost-of-implementing-a-comprehensive-hiv-prevention-and-care-program-among-people-who-inject-drugs-in-delhi-india
#9
Mary Philip Sebastian, Aparajita Dasgupta, Lopamudra Ray Saraswati, Asha Singh, Vartika Sharma, Ira Madan, Waimar Tun, Julie Pulerwitz, Ibou Thior, Avina Sarna
BACKGROUND: WHO, UNODC, and UNAIDS recommend a comprehensive package for prevention, treatment, and care of HIV among people who inject drugs (PWID). We describe the uptake of services and the cost of implementing a comprehensive package for HIV prevention, treatment, and care services in Delhi, India. METHODS: A cohort of 3774 PWID were enrolled for a prospective HIV incidence study and provided the comprehensive package: HIV and hepatitis testing and counseling, hepatitis B (HB) vaccination, syndromic management of sexually transmitted infections, clean needles-syringes, condoms, abscess care, and education...
June 14, 2017: Harm Reduction Journal
https://www.readbyqxmd.com/read/28612535/-prediction-and-analysis-of-epitopes-in-clpp2-of-mycobacterium-tuberculosis
#10
Si-Jing Liu, Ming-Juan Jiang, Qi-Kang Pu, Chen-Yan Ren, Lin Su, Xiang Zhang, Chuan Wang
OBJECTIVES: To predict and analyze the antigenic epitopes in Mycobacterium tuberculosis protein caseinolytic protease P2 (clpP2), and explore its possibility to be applied as a new tuberculosis (TB) vaccine and drug development target. METHODS: Secondary structure of clpP2 based on nucleic sequence was predicted by DNA Star software. The homologous sequence conformation were analyzed by Swiss-Model online software. T cells antigenic epitopes were predicted through VaxiPred, and B cell epitopes were predicted by combining use of several different prediction programs, such as ABCpred, COBEPro and BepiPredPred...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28610781/pilot-studies-of-a-human-bcg-challenge-model
#11
Azra Blazevic, Mei Xia, Aldin Turan, Janice Tennant, Daniel F Hoft
Despite the great effort to develop an effective vaccine against tuberculosis (TB) there is currently no reliable and safe human challenge model that can be used for in vivo evaluation of new TB vaccine candidates and/or elucidation of the mechanisms of TB protective immunity. In this study, five volunteers were challenged with BCG intradermally (ID). Swab specimens were collected at multiple time points from the vaccination site pre- and post-vaccination to quantitate mycobacterial shedding as a surrogate of in vivo mycobacterial immunity...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28608729/accelerating-tuberculosis-vaccine-trials-with-diagnostic-and-prognostic-biomarkers
#12
Stefan H E Kaufmann, January Weiner, Jeroen Maertzdorf
The most recent estimates on tuberculosis (TB) morbidity and mortality reveal that the global disease burden is even higher than previously assumed. Better drugs, diagnostics and vaccines are major requirements to control the ongoing TB pandemic. The high complexity of the infectious process and the underlying pathology, however, challenge elucidation of protective immune mechanisms at the various stages towards active TB disease, which need to be understood for rational design of novel intervention measures...
June 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28604170/efficacy-of-mycobacterium-vaccae-immunotherapy-for-patients-with-tuberculosis-a-systematic-review-and-meta-analysis
#13
Chen-Yi Huang, Wen-Yeh Hsieh
Tuberculosis (TB) is a significant cause of illness and death worldwide. Immunotherapy has been investigated in the treatment of TB. The purpose of this study was to perform a meta-analysis investigating the effectiveness of the M. vaccae vaccine. Medline, Cochrane, EMBASE, and Google Scholar were searched until November 5, 2015 using the keywords: tuberculosis, pulmonary TB, therapeutic vaccines, immunotherapy, M. vaccae, sputum smear. Randomized controlled trials (RCTs) or 2-arm prospective studies were included...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28597826/pathology-of-tuberculosis-how-the-pathology-of-human-tuberculosis-informs-and-directs-animal-models
#14
Randall J Basaraba, Robert L Hunter
Tuberculosis (TB) is a chronic inflammatory disease caused by the pathogenic bacterium Mycobacterium tuberculosis. A wide variety of host- and pathogen-associated variables influence the clinical manifestation of TB in different individuals within the human population. As a consequence, the characteristic granulomatous lesions that develop within the lung are heterogeneous in size and cellular composition. Due to the lack of appropriate tissues from human TB patients, a variety of animal models are used as surrogates to study the basic pathogenesis and to test experimental vaccines and new drug therapies...
June 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28588287/identification-and-evaluation-of-the-novel-immunodominant-antigen-rv2351c-from-mycobacterium-tuberculosis
#15
Xuezhi Wang, Shuangshuang Chen, Yongjuan Xu, Huajun Zheng, Tongyang Xiao, Yuqing Li, Xing Chen, Mingxiang Huang, Haifeng Zhang, Xijing Fang, Yi Jiang, Machao Li, Haican Liu, Kanglin Wan
There is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (TB) and the efficacy of the TB vaccine to control the disease worldwide. In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (MTB)-specific antigen, Rv2351c, from region of difference (RD) 7 of the MTB genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. Twenty T-cell epitopes were identified using TEpredict and prediction tools from the Immune Epitope Database and Analysis Resource...
June 7, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28588268/optimisation-of-a-murine-splenocyte-mycobacterial-growth-inhibition-assay-using-virulent-mycobacterium-tuberculosis
#16
Christina Jensen, Line Lindebo Holm, Erik Svensson, Claus Aagaard, Morten Ruhwald
In the absence of a validated correlate of protection or robust animal models for human tuberculosis, Mycobacterial growth inhibition assays (MGIAs) aim to assess vaccines ability to inhibit mycobacterial growth in-vitro. We optimised a reproducible murine splenocyte MGIA based on in-vitro infection with virulent Mycobacterium tuberculosis (M.tb) Erdman. We identified splenocyte viability as a problem in state-of-art MGIA protocols, which can be improved by simple changes in culture conditions (viability increase from 21% to 46% at last day of culture)...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#17
Susheel K Singh, Susan Thrane, Christoph M Janitzek, Morten A Nielsen, Thor G Theander, Michael Theisen, Ali Salanti, Adam F Sander
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28572807/a-new-adjuvant-mtom-mediates-mycobacterium-tuberculosis-subunit-vaccine-to-enhance-th1-type-t-cell-immune-responses-and-il-2-t-cells
#18
Qi Yu, Xiaochun Wang, Xionglin Fan
The only licensed vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cannot prevent the prevalence of tuberculosis (TB), which remains a major public health problem worldwide. A more effective TB vaccine than BCG is urgently needed. Subunit vaccine is a promising strategy, and suitable adjuvants will benefit the development of effective TB subunit vaccines. MTO, consisting of monophosphoryl lipid A (MPLA), trehalose-6,6'-dibehenate (TDB), and MF59, was developed as an adjuvant of TB vaccine because of its ability to evoke the Th1-type T cell responses, while it is insufficient to induce single and multifunctional IL-2(+) T cells and has a limited ability to confer protection against Mycobacterium tuberculosis infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28570574/the-dynamics-of-immune-responses-to-mycobacterium-tuberculosis-during-different-stages-of-natural-infection-a-longitudinal-study-among-greenlanders
#19
Sascha Wilk Michelsen, Bolette Soborg, Lars Jorge Diaz, Soren Tetens Hoff, Else Marie Agger, Anders Koch, Ida Rosenkrands, Jan Wohlfahrt, Mads Melbye
OBJECTIVE: Understanding human immunity to Mycobacterium tuberculosis (Mtb) during different stages of infection is important for development of an effective tuberculosis (TB) vaccine. We aimed to evaluate immunity to Mtb infection by measuring immune responses to selected Mtb antigens expressed during different stages of infection over time and to observe sustainability of immunity. METHODS: In a cohort study comprising East Greenlanders aged 17-22 years (2012 to 2014) who had either; undetectable Mtb infection, ongoing or prior Mtb infection at enrolment, we measured immunity to 15 antigens over a one-year period...
2017: PloS One
https://www.readbyqxmd.com/read/28569168/construct-design-production-and-characterization-of-plasmodium-falciparum-48-45-r0-6c-subunit-protein-produced-in-lactococcus-lactis-as-candidate-vaccine
#20
Susheel K Singh, Will Roeffen, Ulrik H Mistarz, Bishwanath Kumar Chourasia, Fen Yang, Kasper D Rand, Robert W Sauerwein, Michael Theisen
BACKGROUND: The sexual stages of Plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. The cysteine-rich Pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission. However, clinical Pfs48/45 sub-unit vaccine development has been hampered by the inability to produce high yields of recombinant protein as the native structure is required for the induction of functional transmission-blocking (TB) antibodies...
May 31, 2017: Microbial Cell Factories
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