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TB vaccines

Neng Song, Yang Tan, Lingyun Zhang, Wei Luo, Qing Guan, Ming-Zhe Yan, Ruiqi Zuo, Weixiang Liu, Feng-Ling Luo, Xiao-Lian Zhang
Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M...
April 24, 2018: Emerging Microbes & Infections
Yingmei Fu, Wenjing Li, Zheng Wu, Yuanmeihui Tao, Xinyang Wang, Jing Wei, Peidong Jiang, Jinyin Wu, Zhiwei Zhang, Wenli Zhang, Jizi Zhao, Fengmin Zhang
Bacterial small RNA (sRNA) has been shown to play an important role in control of bacteria virulence, stress response and physiological metabolism by post-transcriptional regulation of gene expression. However, there were few reports about bacterial sRNA as a biomarker of infection. To test the potential role of sRNA in indicating infection of Mycobacterium tuberculosis, total RNA were extracted from the filtrated bacterial cultural supernatant. After synthesis of cDNA by reverse transcription, four Mycobacterial sRNAs including ASdes, ASpks, AS1726, and AS1890, which have been experimentally confirmed by Kristine B in the year of 2009, were detected by real time PCR...
April 21, 2018: Biochemical and Biophysical Research Communications
Sienna R Craig, Timothy Lahey, Apoorva Dixit, C Fordham von Reyn
BACKGROUND: The current vaccine against tuberculosis, BCG, is effective when given in most TB-endemic countries at birth but has diminished efficacy against pulmonary TB after 15-20 years. As a result, new booster vaccines for adolescents and adults are being developed to realize the World Health Organization target of global elimination of TB by 2035. Multiple TB candidates thus are in active clinical development. METHODS: One of these, DAR-901, is advancing in human clinical trials...
April 23, 2018: BMC Public Health
Gina R Webster, Craig van Dolleweerd, Thais Guerra, Szymon Stelter, Sven Hofmann, Mi-Young Kim, Audrey Y-H Teh, Gil Reynolds Diogo, Alastair Copland, Mathew Paul, Peter Hart, Rajko Reljic, Julian K-C Ma
In this study, a strategy based on polymeric immunoglobulin G scaffolds (PIGS), was used to produce a vaccine candidate for Mycobacterium tuberculosis. A genetic fusion construct comprising genes encoding the mycobacterial Ag85B antigen, an immunoglobulin γ-chain fragment and the tailpiece from immunoglobulin μ chain was engineered. Expression was attempted in Chinese Hamster Ovary (CHO) cells and in Nicotiana benthamiana. The recombinant protein assembled into polymeric structures (TB-PIGS) in N. benthamiana, similar in size to polymeric IgM...
April 23, 2018: Plant Biotechnology Journal
Wei Luo, Zilu Qu, Lingyun Zhang, Yan Xie, Fengling Luo, Yang Tan, Qin Pan, Xiao-Lian Zhang
There is a need to develop protective vaccines against tuberculosis (TB). Recently, we identified an immunodominant T-cell antigen, Rv2645, from the region of deletion 13 (RD13) of M. tuberculosis (M. tb) H37Rv, which is absent in Bacille Calmette-Guérin (BCG). Here, a recombinant BCG expressing Rv2645, namely, BCG::Rv2645, was constructed. Compared to BCG, we found that BCG::Rv2645 improved the antigen presentation capacity of dendritic cells (DCs) and elicited much stronger Th1 and Th17 responses, higher CD44high CD62low effector memory CD4+ T cells (TEM ), and fewer T regulated cells (Treg) and regulatory B10 in mice...
April 19, 2018: Vaccine
Sarah Gildea, Marie Garvey, Pamela Lyons, Rachel Lyons, Jacinta Gahan, Cathal Walsh, Ann Cullinane
Equine influenza (EI) outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB) and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were undertaken, and the diagnostic effectiveness of a TaqMan RT-PCR assay was demonstrated in regularly-vaccinated and sub-clinically-affected horses. Epidemiological data and repeat clinical samples were collected from 305 horses, of which 40% were reported as clinically affected, 39% were identified as confirmed cases and 11% were sub-clinically affected...
April 17, 2018: Pathogens
Renate Richardus, Anouk van Hooij, Susan J F van den Eeden, Louis Wilson, Korshed Alam, Jan Hendrik Richardus, Annemieke Geluk
Background: Notwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations...
2018: Frontiers in Immunology
Magdalena Druszczynska, Sebastian Wawrocki, Rafal Szewczyk, Wieslawa Rudnicka
Tuberculosis (TB) remains an escalating problem worldwide. The current diagnostic methods do not always guarantee reliable diagnosis. TB treatment is a time-consuming process that requires the use of several chemotherapeutics, to which mycobacteria are becoming increasingly resistant. This article focuses on the potential utility of biomarkers of mycobacterial origin with potential implications for TB diagnosis. Properly standardized indicators could become new diagnostic tools, improving and streamlining the identification of Mycobacterium tuberculosis infection and the implementation of appropriate therapy...
December 2017: Indian Journal of Medical Research
Elena Stylianou, Rachel Harrington-Kandt, Julia Beglov, Naomi Bull, Nawamin Pinpathomrat, Gwendolyn M Swarbrick, Deborah A Lewinsohn, David M Lewinsohn, Helen McShane
The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( M.tb ), is urgently needed. The only currently available vaccine, BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognised during the course of human infection...
April 16, 2018: Infection and Immunity
César Pedroza-Roldán, Mario Alberto Flores-Valdez
Tuberculosis (TB) remains a major challenge in public health worldwide. Until today, the only widely used and approved vaccine is the Mycobacterium bovis bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of protection against the active, pulmonary form of tuberculosis, and practically none against the latent form of TB infection. This disparity in protection has been extensively studied, and for this reason, several groups have focused their research on the quest for attenuated vaccines based on M...
August 31, 2017: Pathogens and Disease
Jacqueline M Achkar, Rafael Prados-Rosales
A more effective vaccine to control tuberculosis (TB), a major global public health problem, is urgently needed. Current vaccine candidates focus predominantly on eliciting cell-mediated immunity but other arms of the immune system also contribute to protection against TB. We review here recent studies that enhance our current knowledge of antibody-mediated functions against Mycobacterium tuberculosis. These findings, which contribute to the increasing evidence that antibodies have a protective role against TB, include demonstrations that firstly distinct human antibody Fc glycosylation patterns, found in latent M...
April 12, 2018: Current Opinion in Immunology
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, James A Triccas
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, yet current control strategies, including the existing BCG vaccine, have had little impact on disease control. CysVac2, a fusion protein comprising stage-specific Mycobacterium tuberculosis antigens, provided superior protective efficacy against chronic M. tuberculosis infection in mice, compared to BCG. To determine if the delivery of CysVac2 in the context of BCG could improve BCG-induced immunity and protection, we generated a recombinant strain of BCG overexpressing CysVac2 (rBCG:CysVac2)...
April 4, 2018: Vaccine
Seunga Choi, Han-Gyu Choi, JaeHwi Lee, Ki-Won Shin, Hwa-Jung Kim
Tuberculosis remains a serious health problem worldwide. Characterization of the dendritic cell (DC)-activating mycobacterial proteins has driven the development of effective TB vaccine candidates besides improving the understanding of immune responses. Some studies have emphasized the essential role of protein Rv2220 from M. tuberculosis in mycobacterial growth. Nonetheless, little is known about cellular immune responses to Rv2220. In this study, our aim was to test whether protein Rv2220 induces maturation and activation of DCs...
March 31, 2018: Cellular Immunology
Zakeya A Bukhary, Soliman M Amer, Magdy M Emara, Mohammad E Abdalla, Sahar A Ali
BACKGROUND: Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). OBJECTIVE: Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement...
March 2018: Annals of Saudi Medicine
Emily J Strong, Nicholas P West
The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential for disseminated TB in young children its disease protection rates in adults is highly variable while it confers little protection against latent TB. With these limitations a new vaccine is desperately needed. We investigated the efficacy of three members of the mycobacterial membrane protein Large (MmpL) family as potential subunit vaccines for TB. MmpLs are large, multifunctional integral membrane proteins, and as such are recalcitrant to purification...
April 4, 2018: Scientific Reports
World Health Organization
This article presented the World Health Organization's (WHO) recommendations on the use of on Bacille Calmette-Guérin (BCG) vaccine excerpted from the BCG vaccines: WHO position paper - February 2018 published in the Weekly Epidemiological Record [1]. This position paper replaces the 2004 WHO position paper on Bacille Calmette-Guérin (BCG) vaccine [2] and the 2007 WHO revised BCG vaccination guidelines for infants at risk for human immunodeficiency virus (HIV) infection [3]. It incorporates recent developments in the tuberculosis (TB) field, provides revised guidance on the immunization of children infected with HIV, and re-emphasizes the importance of the birth dose...
March 30, 2018: Vaccine
H Muflihah, M Flórido, L C W Lin, Y Xia, J A Triccas, J Stambas, W J Britton
Tuberculosis (TB) infection affects a quarter of the global population resulting in a large burden of TB disease and mortality. The long-term control of TB requires vaccines with greater efficacy and durability than the current Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary immunization may increase and prolong immunity at the site of Mycobacterium tuberculosis infection. We have investigated recombinant influenza A viruses (rIAVs) expressing the p25 CD4+ T cell epitope of M. tuberculosis Ag85B240-254 for single and sequential immunization against M...
March 27, 2018: Vaccine
Wenping Gong, Yan Liang, Xueqiong Wu
Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10 causes of death worldwide. TB results in more fatalities than multi-drug resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the prevention and control of infectious diseases. Unfortunately, the only licensed preventive vaccine against TB, bacilli Calmette-Guérin (BCG), is ineffective for prevention of pulmonary TB in adults. Therefore, it is very important to develop novel vaccines for TB prevention and control...
March 30, 2018: Human Vaccines & Immunotherapeutics
Huichang Huang, Feifei Wang, Enzhuo Yang, Honghai Wang, Peng Gao, Hongbo Shen
The emergence of drug-resistant tuberculosis (TB) and HIV-TB co-infection fuels an urgent need to develop novel therapeutic approaches, including therapeutic vaccines. Therapeutic vaccines have been proven to be a good strategy by inducing antigen specific immune responses against TB infection. In the present study, a recombinant plasmid based on lentiviral vector expressing fusion antigen Ag85B-Rv3425 (A3), and was constructed the immunogenicity and treatment effects in TB mice were assessed. The results showed that A3 delivered by the plasmid could be expressed appropriately in vivo and induced higher production of tumor necrosis factor-α and interleukin-2 compared with A3 recombinant protein in mice...
March 2018: Experimental and Therapeutic Medicine
Katherine Floyd, Philippe Glaziou, Alimuddin Zumla, Mario Raviglione
Tuberculosis is the number one cause of death from infectious disease globally and drug-resistant forms of the disease are a major risk to global health security. On the occasion of World Tuberculosis Day (March 24, 2018), we provide an up-to-date review of the status of the tuberculosis epidemic, recommended diagnostics, drug treatments and vaccines, progress in delivery of care and prevention, progress in research and development, and actions needed to accelerate progress. This Review is presented in the context of the UN Sustainable Development Goals and WHO's End TB Strategy, which share the aim of ending the global tuberculosis epidemic...
April 2018: Lancet Respiratory Medicine
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