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https://www.readbyqxmd.com/read/29675017/-de-novo-fatty-acid-synthesis-during-mycobacterial-infection-is-a-prerequisite-for-the-function-of-highly-proliferative-t-cells-but-not-for-dendritic-cells-or-macrophages
#1
Philipp Stüve, Lucía Minarrieta, Hanna Erdmann, Catharina Arnold-Schrauf, Maxine Swallow, Melanie Guderian, Freyja Krull, Alexandra Hölscher, Peyman Ghorbani, Jochen Behrends, Wolf-Rainer Abraham, Christoph Hölscher, Tim D Sparwasser, Luciana Berod
Mycobacterium tuberculosis ( Mtb ), the causative agent of human tuberculosis, is able to efficiently manipulate the host immune system establishing chronic infection, yet the underlying mechanisms of immune evasion are not fully understood. Evidence suggests that this pathogen interferes with host cell lipid metabolism to ensure its persistence. Fatty acid metabolism is regulated by acetyl-CoA carboxylase (ACC) 1 and 2; both isoforms catalyze the conversion of acetyl-CoA into malonyl-CoA, but have distinct roles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670610/neonatal-immunization-rationale-current-state-and-future-prospects
#2
REVIEW
Elizabeth Whittaker, David Goldblatt, Peter McIntyre, Ofer Levy
Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29627232/protective-efficacy-of-recombinant-bcg-over-expressing-protective-stage-specific-antigens-of-mycobacterium-tuberculosis
#3
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
https://www.readbyqxmd.com/read/29602704/sequential-pulmonary-immunization-with-heterologous-recombinant-influenza-a-virus-tuberculosis-vaccines-protects-against-murine-m-tuberculosis-infection
#4
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
https://www.readbyqxmd.com/read/29595510/safety-and-immunogenicity-of-the-novel-tuberculosis-vaccine-id93-gla-se-in-bcg-vaccinated-healthy-adults-in-south-africa-a-randomised-double-blind-placebo-controlled-phase-1-trial
#5
Adam Penn-Nicholson, Michele Tameris, Erica Smit, Tracey A Day, Munyaradzi Musvosvi, Lakshmi Jayashankar, Julie Vergara, Simbarashe Mabwe, Nicole Bilek, Hendrik Geldenhuys, Angelique Kany-Kany Luabeya, Ruth Ellis, Ann M Ginsberg, Willem A Hanekom, Steven G Reed, Rhea N Coler, Thomas J Scriba, Mark Hatherill
BACKGROUND: A vaccine that prevents pulmonary tuberculosis in adults is needed to halt transmission in endemic regions. This trial aimed to assess the safety and immunogenicity of three administrations at varying doses of antigen and adjuvant of an investigational vaccine (ID93 + GLA-SE) compared with placebo in previously BCG-vaccinated healthy adults in a tuberculosis endemic country. METHODS: In this randomised, double-blind, placebo-controlled phase 1 trial, we enrolled HIV-negative, previously BCG-vaccinated adults (aged 18-50 years), with no evidence of previous or current tuberculosis disease, from among community volunteers in the Worcester region of Western Cape, South Africa...
April 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29593708/mucosal-delivery-of-fusion-proteins-with-bacillus-subtilis-spores-enhances-protection-against-tuberculosis-by-bacillus-calmette-gu%C3%A3-rin
#6
Alastair Copland, Gil R Diogo, Peter Hart, Shane Harris, Andy C Tran, Mathew J Paul, Mahavir Singh, Simon M Cutting, Rajko Reljic
Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guérin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29567319/in-silico-design-of-mycobacterium-tuberculosis-epitope-ensemble-vaccines
#7
Preksha Shah, Jaymisha Mistry, Pedro A Reche, Derek Gatherer, Darren R Flower
Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa...
March 19, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29518353/nanoparticle-fusion-protein-complexes-protect-against-mycobacterium-tuberculosis-infection
#8
Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29447423/nk-cells-inhibit-anti-mycobacterium-bovis-bcg-t-cell-responses-and-aggravate-pulmonary-inflammation-in-a-direct-lung-infection-mouse-model
#9
Dongfang Wang, Xiuling Gu, Xiaoman Liu, Songtao Wei, Bin Wang, Min Fang
Tuberculosis remains a threat to public health. The major problem for curing this disease is latent infection, of which the underlying mechanisms are still not fully understood. Previous studies indicate that natural killer (NK) cells do not play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung, and recent studies have revealed that NK cells regulate the adaptive immunity during mycobacterial infection. By using a mouse model of direct lung infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG), we found that the presence of NK cells postponed the priming and activation of T cells after BCG infection...
February 15, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29249639/t-cells-primed-by-live-mycobacteria-versus-a-tuberculosis-subunit-vaccine-exhibit-distinct-functional-properties
#10
Thomas Lindenstrøm, Albanus Moguche, Mie Damborg, Else Marie Agger, Kevin Urdahl, Peter Andersen
Despite inducing strong T cell responses, Mycobacterium tuberculosis (Mtb) infection fails to elicit protective immune memory. As such latently infected or successfully treated Tuberculosis (TB) patients are not protected against recurrent disease. Here, using a mouse model of aerosol Mtb infection, we show that memory immunity to H56/CAF01 subunit vaccination conferred sustained protection in contrast to the transient natural immunity conferred by Mtb infection. Loss of protection to re-infection in natural Mtb memory was temporally linked to an accelerated differentiation of ESAT-6- and to a lesser extent, Ag85B-specific CD4 T cells in both the lung parenchyma and vasculature...
January 2018: EBioMedicine
https://www.readbyqxmd.com/read/29230214/exome-sequencing-identifies-a-novel-map3k14-mutation-in-recessive-atypical-combined-immunodeficiency
#11
Nikola Schlechter, Brigitte Glanzmann, Eileen Garner Hoal, Mardelle Schoeman, Britt-Sabina Petersen, Andre Franke, Yu-Lung Lau, Michael Urban, Paul David van Helden, Monika Maria Esser, Marlo Möller, Craig Kinnear
Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG) vaccination and dissemination in combined immunodeficiencies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230061/boosting-with-recombinant-mva-expressing-m-tuberculosis-%C3%AE-crystallin-antigen-augments-the-protection-imparted-by-bcg-against-tuberculosis-in-guinea-pigs
#12
Prachi Nangpal, Ritika Kar Bahal, Anil K Tyagi
Tuberculosis (TB) is one of the major causes of mortality all over the globe. BCG, the only vaccine available against this disease has been successful in preventing the severe forms of childhood TB. However, the unsatisfactory performance of BCG in controlling the adult pulmonary tuberculosis has made the development of an effective vaccine against M. tuberculosis a prime objective of the TB research. In this study, a genetically stable, marker-free recombinant MVA expressing α-crystallin of M. tuberculosis (rMVA...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29155877/immune-response-profiles-of-calves-following-vaccination-with-live-bcg-and-inactivated-mycobacterium-bovis-vaccine-candidates
#13
E M D L van der Heijden, J Chileshe, J C M Vernooij, C Gortazar, R A Juste, I Sevilla, J E Crafford, V P M G Rutten, A L Michel
Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations...
2017: PloS One
https://www.readbyqxmd.com/read/29148853/multi-stage-subunit-vaccines-against-mycobacterium-tuberculosis-an-alternative-to-the-bcg-vaccine-or-a-bcg-prime-boost
#14
Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Mohsen Tafaghodi, Saman Soleimanpour
More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants...
January 2018: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29140925/mobilization-of-cd4-t-lymphocytes-in-inflamed-mucosa-reduces-pain-in-colitis-mice-toward-a-vaccinal-strategy-to-alleviate-inflammatory-visceral-pain
#15
Lilian Basso, Jérôme Boué, Céline Augé, Céline Deraison, Catherine Blanpied, Nicolas Cenac, Philippe Lluel, Nathalie Vergnolle, Gilles Dietrich
T lymphocytes play a pivotal role in endogenous regulation of inflammatory visceral pain. The analgesic activity of T lymphocytes is dependent on their production of opioids, a property acquired on antigen activation. Accordingly, we investigated whether an active recruitment of T lymphocytes within inflamed colon mucosa via a local vaccinal strategy may counteract inflammation-induced visceral pain in mice. Mice were immunized against ovalbumin (OVA). One month after immunization, colitis was induced by adding 3% (wt/vol) dextran sulfate sodium into drinking water containing either cognate antigen OVA or control antigen bovine serum albumin for 5 days...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29124321/vaccine-responses-in-newborns
#16
REVIEW
Anja Saso, Beate Kampmann
Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants...
November 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29081214/potentiation-of-th1-type-immune-responses-to-mycobacterium-tuberculosis-antigens-in-mice-by-cationic-liposomes-combined-with-de-o-acylated-lipooligosaccharide
#17
Ara Ko, Seo Ri Wui, Ji In Ryu, Yeon Jeong Lee, Do Thi Thu Hien, Inmoo Rhee, Sung Jae Shin, Shin Ae Park, Kwang Sung Kim, Yang Je Cho, Na Gyong Lee
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis . Bacillus Calmette-Guérin (BCG) vaccine is the only TB vaccine currently available, but it is not sufficiently effective in preventing active pulmonary TB or adult infection. With the purpose of developing an improved vaccine against TB that can overcome the limitations of the current BCG vaccine, we investigated whether adjuvant formulations containing de- O -acylated lipooligosaccharide (dLOS) are capable of enhancing the immunogenicity and protective efficacy of TB subunit vaccine...
January 28, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29067283/small-molecule-mediated-restoration-of-mitochondrial-function-augments-anti-mycobacterial-activity-of-human-macrophages-subjected-to-cholesterol-induced-asymptomatic-dyslipidemia
#18
Suman Asalla, Krishnaveni Mohareer, Sharmistha Banerjee
Mycobacterium tuberculosis ( M.tb) infection manifests into tuberculosis (TB) in a small fraction of the infected population that comprises the TB susceptible group. Identifying the factors potentiating susceptibility to TB persistence is one of the prime agenda of TB control programs. Recently, WHO recognized diabetes as a risk factor for TB disease progression. The closely related pathological state of metabolic imbalance, dyslipidemia, is yet another emerging risk factor involving deregulation in host immune responses...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29034213/a-promising-listeria-vectored-vaccine-induces-th1-type-immune-responses-and-confers-protection-against-tuberculosis
#19
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-for-infants-of-human-immunodeficiency-virus-infected-mothers-a-phase-2-randomized-controlled-trial
#20
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 human immunodeficiency virus (HIV)-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis vaccination strategy that protects against tuberculosis 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 × 108 PFU) vs Candin® control, followed by selective, deferred BCG vaccination at age 8 weeks for HIV-uninfected infants and 12 months follow-up for safety and immunogenicity...
February 1, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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