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BCG prime

Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea
BACKGROUND: Innate immune memory or 'trained immunity' has recently been described as an important property of cells of the innate immune system. Due to the increased interest in this important new field of immunological investigation we sought to determine the optimal conditions for an in-vitro experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the Bacille Calmette-Guérin (BCG) vaccine, and oxidized LDL (oxLDL)...
October 12, 2016: Clinical and Vaccine Immunology: CVI
Mangalakumari Jeyanathan, Daniela Damjanovic, Yushi Yao, Jonathan Bramson, Fiona Smaill, Zhou Xing
BACKGROUND:  Whether a candidate TB vaccine induces clinically relevant protective T cell repertoires in humans is not known until the completion of costly efficacy clinical trials. METHODS:  We have developed an integrated immunologic approach to investigate the clinical relevance of a novel TB vaccine-induced T cells in a phase 1 trial. This approach consists of screening for likely dominant T cell epitopes, establishing Ag-specific memory T cell lines for identifying CD8 and CD4 T cell epitopes, determining the ability of vaccine-induced T cells to inhibit mycobacterial growth in infected cells, and examining the genetic diversity of HLA recognition and clinical relevance of identified T cell epitopes...
October 4, 2016: Journal of Infectious Diseases
Jilei Ma, Maopeng Tian, Xionglin Fan, Qi Yu, Yukai Jing, Weihua Wang, Li Li, Zijie Zhou
There is an urgent need for a vaccine against tuberculosis (TB) that is more effective than the current sole licensed option. However, target antigens of Mycobacterium tuberculosis with the vaccine potential remain elusive. Five immunodominant antigens with characteristic expressions at the stages of primary infection (Ag85A), the regulation of nutrition and metabolism when transferring from rapid growth to latency (PhoY2 and Rv3407), latency (Rv2626c), and reactivation (RpfB) were selected to construct the fusion polyprotein WH121, which has better immunogenicity and protection than each multistage antigen...
August 23, 2016: Oncotarget
Hannah J Metcalfe, Sabine Steinbach, Gareth J Jones, Tim Connelley, W Ivan Morrison, Martin Vordermeier, Bernardo Villarreal-Ramos
There is a need to improve the efficacy of Bacille Calmette-Guérin (BCG) vaccination against tuberculosis in humans and cattle. Previously, we found boosting BCG-primed cows with recombinant human type 5 adenovirus expressing antigen 85A (Ad5-85A) increased protection against Mycobacterium bovis infection compared to BCG vaccination alone. The aim of this study was to decipher aspects of the immune response associated with this enhanced protection. We compared BCG-primed Ad5-85A-boosted cattle with BCG-vaccinated cattle...
August 31, 2016: Vaccine
Rachel Pinto, Jonathan K Nambiar, Lisa Leotta, Claudio Counoupas, Warwick J Britton, James A Triccas
The characterisation of mycobacterial factors that influence or modulate the host immune response may aid the development of more efficacious TB vaccines. We have previously reported that Mycobacterium tuberculosis deficient in export of Phthiocerol Dimycocerosates (DIM) (MT103(ΔdrrC)) is more attenuated than wild type M. tuberculosis and provides sustained protective immunity compared to the existing BCG vaccine. Here we sought to define the correlates of immunity associated with DIM deficiency by assessing the impact of MT103(ΔdrrC) delivery on antigen presenting cell (APC) function and the generation of CD4(+) T cell antigen-specific immunity...
July 2016: Tuberculosis
Tsungai Ivai Jongwe, Ros Chapman, Nicola Douglass, Shivan Chetty, Gerald Chege, Anna-Lise Williamson
Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study...
2016: PloS One
Daryan A Kaveh, M Carmen Garcia-Pelayo, Paul R Webb, Esen E Wooff, Véronique S Bachy, Philip J Hogarth
Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes...
July 25, 2016: Vaccine
Aaron Olsen, Yong Chen, Qingzhou Ji, Guofeng Zhu, Aruna Dharshan De Silva, Catherine Vilchèze, Torin Weisbrod, Weimin Li, Jiayong Xu, Michelle Larsen, Jinghang Zhang, Steven A Porcelli, William R Jacobs, John Chan
UNLABELLED: Tumor necrosis factor alpha (TNF) plays a critical role in the control of Mycobacterium tuberculosis, in part by augmenting T cell responses through promoting macrophage phagolysosomal fusion (thereby optimizing CD4(+) T cell immunity by enhancing antigen presentation) and apoptosis (a process that can lead to cross-priming of CD8(+) T cells). M. tuberculosis can evade antituberculosis (anti-TB) immunity by inhibiting host cell TNF production via expression of specific mycobacterial components...
2016: MBio
Subhadra Nandakumar, Sunil Kannanganat, Karen M Dobos, Megan Lucas, John S Spencer, Rama Rao Amara, Bonnie B Plikaytis, James E Posey, Suraj B Sable
Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response...
2016: Scientific Reports
M Carmen Garcia-Pelayo, Daryan A Kaveh, Laura Sibly, Paul R Webb, Naomi C Bull, Simon M Cutting, Philip J Hogarth
Tuberculosis (TB) remains a global pandemic, in both animals and man, and novel vaccines are urgently required. Heterologous prime-boost of BCG represents a promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be an ideal vaccination strategy against bovine TB (bTB), but respiratory vaccination presents a technical challenge in cattle. Inert bacterial spores represent an attractive vaccine vehicle. Therefore we evaluated whether parenterally administered spores are efficacious when used as a BCG boost in a murine model of immunity against Mycobacterium bovis...
May 2016: Tuberculosis
Hadi Farsiani, Arman Mosavat, Saman Soleimanpour, Hamid Sadeghian, Mohammad Reza Akbari Eydgahi, Kiarash Ghazvini, Mojtaba Sankian, Ehsan Aryan, Saeid Amel Jamehdar, Seyed Abdolrahim Rezaee
Tuberculosis (TB) remains a major global health threat despite chemotherapy and Bacilli Calmette-Guérin (BCG) vaccination. Therefore, a safer and more effective vaccine against TB is urgently needed. This study evaluated the immunogenicity of a recombinant fusion protein consisting of early secreted antigenic target protein 6 kDa (ESAT-6), culture filtrate protein 10 kDa (CFP-10) and the Fc-domain of mouse IgG2a as a novel subunit vaccine. The recombinant expression vectors (pPICZαA-ESAT-6:CFP-10:Fcγ2a and pPICZαA-ESAT-6:CFP-10:His) were transferred into Pichia pastoris...
June 21, 2016: Molecular BioSystems
Owais Mohammad, Jagdeep Kaur, Gurpreet Singh, Syed Mohd Faisal, Asim Azhar, Mohd Ahmar Rauf, Umesh Dutt Gupta, Pushpa Gupta, Rahul Pal, Swaleha Zubair
In general, the members of Lip gene family of Mycobacterium tuberculosis evoke strong immune response in the host. Keeping this fact into consideration, we investigated role of Rv3203, a cell wall associated protein with lipolytic activity, in imparting protection against experimental murine tuberculosis. The data of the present study suggested that archaeosome encapsulated Rv3203 induce strong lymphocyte proliferation, up-regulated Th-1 biased cytokines profile, increased expression of co-stimulatory markers on both antigen presenting cells and T lymphocytes...
2016: PloS One
Martin Gengenbacher, Peggy Kaiser, Stefanie Schuerer, Doris Lazar, Stefan H E Kaufmann
The tuberculosis vaccine BCG ΔureC::hly is the most advanced BCG replacement candidate in phase II clinical development. Here we assess the protective capacity of the construct administered to mice as homologous prime-boost vaccine prior Mycobacterium tuberculosis infection and as post-exposure vaccine. Multiple immunization did not improve the superior protection of BCG ΔureC::hly over BCG. Animals with subclinical tuberculosis were better protected when vaccinated with BCG ΔureC::hly as compared to BCG...
May 2016: Microbes and Infection
Clair M Gardiner, Kingston H G Mills
Immunological memory mediated by antigen-specific T and B cells is the foundation of adaptive immunity and is fundamental to the heightened and rapid protective immune response induced by vaccination or following re-infection with the same pathogen. While the innate immune system has classically been considered to be non-specific and devoid of memory, it now appears that it can be trained following exposure to microbes or their products and that this may confer a form of memory on innate immune cells. The evidence for immunological memory outside of T and B cells has been best established for natural killer (NK) cells, where it has been known for decades that NK cells have heighten responses following immunological re-challenge...
August 2016: Seminars in Immunology
Dongqing Gu, Wei Chen, Youjun Mi, Xueli Gong, Tao Luo, Lang Bao
Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures...
April 2016: Acta Biochimica et Biophysica Sinica
Alice Minhinnick, Iman Satti, Stephanie Harris, Morven Wilkie, Sharon Sheehan, Lisa Stockdale, Zita-Rose Manjaly Thomas, Raquel Lopez-Ramon, Ian Poulton, Alison Lawrie, Samantha Vermaak, Alexandre Le Vert, Judith Del Campo, Fergal Hill, Paul Moss, Helen McShane
INTRODUCTION: There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. METHODS: In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C)...
March 8, 2016: Vaccine
Arman Mosavat, Saman Soleimanpour, Hadi Farsiani, Hamid Sadeghian, Kiarash Ghazvini, Mojtaba Sankian, Saeid Amel Jamehdar, Seyed Abdolrahim Rezaee
Tuberculosis (TB) remains a major health problem worldwide. Currently, the Bacilli Calmette-Guérin (BCG) is the only available licensed TB vaccine, which has low efficacy in protection against adult pulmonary TB. Therefore, the development of a safe and effective vaccine against TB needs global attention. In the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (CFP-10) and heat shock protein X (HspX) of Mycobacterium tuberculosis fused to the Fc domain of mouse IgG2a as a selective delivery system for antigen-presenting cells (APCs) was produced and its immunogenicity assessed...
April 2016: Infection, Genetics and Evolution
Katja Obieglo, Xiaogang Feng, Vishnu Priya Bollampalli, Isabel Dellacasa-Lindberg, Cajsa Classon, Markus Österblad, Helena Helmby, James P Hewitson, Rick M Maizels, Antonio Gigliotti Rothfuchs, Susanne Nylén
Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette-Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4(+) T cell priming in both the spleen and skin-draining lymph nodes...
March 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Enzhuo Yang, Jin Gu, Feifei Wang, Honghai Wang, Hongbo Shen, Zheng W Chen
Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425...
April 2016: Microbial Pathogenesis
Eun Young Nam, Sun Hee Na, Se Yong Kim, Doran Yoon, Chung-Jong Kim, Kyoung Un Park, Seung-Kee Min, Sang Eun Lee, Pyoeng Gyun Choe
A 70-year-old man presented with lower back pain and cyanotic changes in his left lower extremity. He was diagnosed with infected aortic aneurysm and infectious spondylitis. He had received intravesical Bacillus Calmette-Guérin (BCG) therapy up to 1 month before the onset of symptoms. The aneurysm was excised and an aorto-biiliac interposition graft was performed. Mycobacterium tuberculosis complex was cultured in the surgical specimens. Real-time polymerase chain reaction (PCR) targeting the senX3-regX3 region, and multiplex PCR using dual-priming oligonucleotide primers targeting the RD1 gene, revealed that the organism isolated was Mycobacterium bovis BCG...
December 2015: Infection & Chemotherapy
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