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https://www.readbyqxmd.com/read/29148853/multi-stage-subunit-vaccines-against-mycobacterium-tuberculosis-an-alternative-to-the-bcg-vaccine-or-a-bcg-prime-boost
#1
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 17, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29140925/mobilization-of-cd4-t-lymphocytes-in-inflamed-mucosa-reduces-pain-in-colitis-mice-towards-a-vaccinal-strategy-to-alleviate-inflammatory-visceral-pain
#2
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 upon 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% (w/v) Dextran Sulfate Sodium (DSS) into drinking water containing either cognate antigen OVA or control antigen BSA for 5 days...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29124321/vaccine-responses-in-newborns
#3
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 9, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29081214/potentiation-of-th1-type-immune-responses-to-m-tuberculosis-antigens-in-mice-by-cationic-liposomes-combined-with-de-o-acylated-lipooligosaccharide
#4
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
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
#5
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
#6
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-bcg-for-infants-of-hiv-infected-mothers-a-phase-2-randomized-controlled-trial
#7
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
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#8
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
https://www.readbyqxmd.com/read/28974092/poly-i-c-encapsulating-nanoparticles-enhance-innate-immune-responses-to-the-tuberculosis-vaccine-bacille-calmette-gu%C3%A3-rin-bcg-via-synergistic-activation-of-innate-immune-receptors
#9
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
https://www.readbyqxmd.com/read/28808204/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#10
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
https://www.readbyqxmd.com/read/28768668/a-combination-of-recombinant-mycobacterium-bovis-bcg-strains-expressing-pneumococcal-proteins-induces-cellular-and-humoral-immune-responses-and-protects-against-pneumococcal-colonization-and-sepsis
#11
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
https://www.readbyqxmd.com/read/28728855/tissue-plasminogen-activator-tpa-signal-sequence-enhances-immunogenicity-of-mva-based-vaccine-against-tuberculosis
#12
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
https://www.readbyqxmd.com/read/28711483/a-multistage-subunit-vaccine-effectively-protects-mice-against-primary-progressive-tuberculosis-latency-and-reactivation
#13
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
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#14
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
https://www.readbyqxmd.com/read/28546518/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#15
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...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28498853/safety-and-immunogenicity-of-an-inactivated-whole-cell-tuberculosis-vaccine-booster-in-adults-primed-with-bcg-a-randomized-controlled-trial-of-dar-901
#16
RANDOMIZED CONTROLLED TRIAL
C Fordham von Reyn, Timothy Lahey, Robert D Arbeit, Bernard Landry, Leway Kailani, Lisa V Adams, Brenda C Haynes, Todd Mackenzie, Wendy Wieland-Alter, Ruth I Connor, Sue Tvaroha, David A Hokey, Ann M Ginsberg, Richard Waddell
BACKGROUND: Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic. METHODS: We performed a single site, randomized, double-blind, controlled, Phase 1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the United States...
2017: PloS One
https://www.readbyqxmd.com/read/28476627/-the-impact-of-mycobacterium-tuberculosis-immune-evasion-on-protective-immunity-implications-for-tb-vaccine-design-meeting-report
#17
Cesar Boggiano, Katrin Eichelberg, Lakshmi Ramachandra, Jaqueline Shea, Lalita Ramakrishnan, Samuel Behar, Joel D Ernst, Steven A Porcelli, Markus Maeurer, Hardy Kornfeld
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB...
June 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28453555/multi-subunit-bcg-booster-vaccine-gamtbvac-assessment-of-immunogenicity-and-protective-efficacy-in-murine-and-guinea-pig-tb-models
#18
A P Tkachuk, V A Gushchin, V D Potapov, A V Demidenko, V G Lunin, A L Gintsburg
New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models...
2017: PloS One
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#19
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep Ma Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector uses an antibiotic resistance-free mechanism for plasmid selection and maintenance...
August 3, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28342639/sendai-virus-mucosal-vaccination-establishes-lung-resident-memory-cd8%C3%A2-t-cell-immunity-and-boosts-bcg-primed-protection-against-tb-in-mice
#20
Zhidong Hu, Ka-Wing Wong, Hui-Min Zhao, Han-Li Wen, Ping Ji, Hui Ma, Kang Wu, Shui-Hua Lu, Feng Li, Zhong-Ming Li, Tsugumine Shu, Jian-Qing Xu, Douglas B Lowrie, Xiao-Yong Fan
Accumulating evidence has shown the protective role of CD8(+) T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8(+) T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice...
May 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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