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BCG prime

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
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 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 M.bovis 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
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...
December 7, 2017: EBioMedicine
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
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
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
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...
November 22, 2017: Expert Review of Vaccines
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
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
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...
October 31, 2017: Journal of Microbiology and Biotechnology
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
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
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
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
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...
November 6, 2017: Molecular Pharmaceutics
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
July 13, 2017: Journal of Biomedical Research
Cibelly Goulart, Dunia Rodriguez, Alex I Kanno, Thiago Rojas Converso, Ying-Jie Lu, Richard Malley, Luciana C C Leite
Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children...
October 2017: Clinical and Vaccine Immunology: CVI
Yiming Kou, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, Chunlai Jiang
Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines...
July 17, 2017: Immunology Letters
Jilei Ma, Xindong Teng, Xiaochun Wang, Xionglin Fan, Yaqi Wu, Maopeng Tian, Zijie Zhou, Longmeng Li
Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed...
August 2017: EBioMedicine
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
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